Metastatic Breast Cancer

Results from a new phase IIb, 2x2 randomized, open-label trial (GeparSEPTO) showed no improvement in pathologic complete response (pCR) rates when the RANKL inhibitor denosumab was added to anthracycline/taxane-based neoadjuvant chemotherapy in the treatment of primary breast cancer. The study found that a weekly anthracycline/taxane-based neoadjuvant chemotherapy led to improved pCR compared to an every 3-week schedule both overall and in patients with triple-negative breast cancer (TNBC), though it was associated with greater toxicity.

“Currently, I do not see a place for antiosteolytic agents as part of the neoadjuvant therapy in breast cancer,” said lead author Sibylle Loibl, MD, PhD, who is a breast cancer researcher at Goethe (Germany) University. The researchers can’t exclude the possibility of a long-term benefit, and patients will be followed for disease-free and overall survival.

The disappointing result comes after previous studies of denosumab or bisphosphonates as additions to adjuvant therapy reduced metastases and increased survival in breast cancer, prompting optimism that the agents might improve pCR rates and improve survival rates in the neoadjuvant setting.

The failure may be because of the shorter treatment duration, and it’s possible that pCR is not the best endpoint to study for a drug that has long-acting potential, according to Dr. Loibl.

Patients were randomized to 120 mg denosumab every 4 weeks for six cycles or to receive no supplementary treatment. Patients with or without denosumab either received nab-paclitaxel 125 mg/m² weekly for 12 weeks or on days 1 and 8 every 3 weeks, over four cycles (eight total doses), then epirubicin/cyclophosphamide, 90/600 mg/m² (every 2 and 3 weeks, respectively). Patients with triple-negative breast cancer also received carboplatin. Patients with ERBB2-positive breast cancer received the trastuzumab biosimilar ABP980 plus pertuzumab.

The study included 780 patients (1 male), with a median age of 49.0 years. There was no difference in pCR among denosumab recipients and nonrecipients (41.0% versus 42.8%; P = .58). Weekly nab-paclitaxel led to a higher pCR rate than a schedule of days 1 and 8 every 3 weeks (44.9% versus 39.0%; P = .06, significance level of alpha = .10). Among subgroups, there was only a difference in pCR rates among those with TNBC (60.4% versus 50.0%; P = .06). Grade 3-4 toxic effects were similar regardless of denosumab exposure, but nonhematologic grade 3-4 toxicity was higher with weekly nab-paclitaxel (33.7% versus 24.1%; P = .004).

“The overall pCR difference (with nab-paclitaxel as neoadjuvant chemotherapy) seems small, but looking at the data from the GeparSEPTO study we would expect a transformation into a better invasive disease-free survival. Looking specifically into patients with TNBC, there is clear pCR increase by using the weekly regimen. With just over 60%, this is the highest pCR rate reported so far for a chemotherapy-only regimen. I would prefer to use nab-paclitaxel also in early breast cancer and would use the weekly regimen for women with TNBC who are at high risk,” Dr. Loibl said.

The study was limited by an imbalance of tumor subtypes between the treatment groups. The authors wrote that the results should guide further research, but nab-paclitaxel should not currently be viewed as a standard neoadjuvant treatment of breast cancer.

The study was funded by the German Breast Group, Bristol Myers Squibb, and Amgen. Dr. Loibl has served on the advisory boards or given lectures for AbbVie, Amgen, Bayer, Celgene, EirGenix, GSK, Lilly, Merck, Puma, Seagen, AstraZeneca, Daiichi Sankyo, Novartis, Pierre Fabre, Prime/Medscape, Bristol Myers Squibb, Chugai, Ipsen, Roche, and Samsung. She also holds a related patent.

Results from a new phase IIb, 2x2 randomized, open-label trial (GeparSEPTO) showed no improvement in pathologic complete response (pCR) rates when the RANKL inhibitor denosumab was added to anthracycline/taxane-based neoadjuvant chemotherapy in the treatment of primary breast cancer. The study found that a weekly anthracycline/taxane-based neoadjuvant chemotherapy led to improved pCR compared to an every 3-week schedule both overall and in patients with triple-negative breast cancer (TNBC), though it was associated with greater toxicity.

“Currently, I do not see a place for antiosteolytic agents as part of the neoadjuvant therapy in breast cancer,” said lead author Sibylle Loibl, MD, PhD, who is a breast cancer researcher at Goethe (Germany) University. The researchers can’t exclude the possibility of a long-term benefit, and patients will be followed for disease-free and overall survival.

The disappointing result comes after previous studies of denosumab or bisphosphonates as additions to adjuvant therapy reduced metastases and increased survival in breast cancer, prompting optimism that the agents might improve pCR rates and improve survival rates in the neoadjuvant setting.

The failure may be because of the shorter treatment duration, and it’s possible that pCR is not the best endpoint to study for a drug that has long-acting potential, according to Dr. Loibl.

Patients were randomized to 120 mg denosumab every 4 weeks for six cycles or to receive no supplementary treatment. Patients with or without denosumab either received nab-paclitaxel 125 mg/m² weekly for 12 weeks or on days 1 and 8 every 3 weeks, over four cycles (eight total doses), then epirubicin/cyclophosphamide, 90/600 mg/m² (every 2 and 3 weeks, respectively). Patients with triple-negative breast cancer also received carboplatin. Patients with ERBB2-positive breast cancer received the trastuzumab biosimilar ABP980 plus pertuzumab.

The study included 780 patients (1 male), with a median age of 49.0 years. There was no difference in pCR among denosumab recipients and nonrecipients (41.0% versus 42.8%; P = .58). Weekly nab-paclitaxel led to a higher pCR rate than a schedule of days 1 and 8 every 3 weeks (44.9% versus 39.0%; P = .06, significance level of alpha = .10). Among subgroups, there was only a difference in pCR rates among those with TNBC (60.4% versus 50.0%; P = .06). Grade 3-4 toxic effects were similar regardless of denosumab exposure, but nonhematologic grade 3-4 toxicity was higher with weekly nab-paclitaxel (33.7% versus 24.1%; P = .004).

“The overall pCR difference (with nab-paclitaxel as neoadjuvant chemotherapy) seems small, but looking at the data from the GeparSEPTO study we would expect a transformation into a better invasive disease-free survival. Looking specifically into patients with TNBC, there is clear pCR increase by using the weekly regimen. With just over 60%, this is the highest pCR rate reported so far for a chemotherapy-only regimen. I would prefer to use nab-paclitaxel also in early breast cancer and would use the weekly regimen for women with TNBC who are at high risk,” Dr. Loibl said.

The study was limited by an imbalance of tumor subtypes between the treatment groups. The authors wrote that the results should guide further research, but nab-paclitaxel should not currently be viewed as a standard neoadjuvant treatment of breast cancer.

The study was funded by the German Breast Group, Bristol Myers Squibb, and Amgen. Dr. Loibl has served on the advisory boards or given lectures for AbbVie, Amgen, Bayer, Celgene, EirGenix, GSK, Lilly, Merck, Puma, Seagen, AstraZeneca, Daiichi Sankyo, Novartis, Pierre Fabre, Prime/Medscape, Bristol Myers Squibb, Chugai, Ipsen, Roche, and Samsung. She also holds a related patent.

Results from a new phase IIb, 2x2 randomized, open-label trial (GeparSEPTO) showed no improvement in pathologic complete response (pCR) rates when the RANKL inhibitor denosumab was added to anthracycline/taxane-based neoadjuvant chemotherapy in the treatment of primary breast cancer. The study found that a weekly anthracycline/taxane-based neoadjuvant chemotherapy led to improved pCR compared to an every 3-week schedule both overall and in patients with triple-negative breast cancer (TNBC), though it was associated with greater toxicity.

“Currently, I do not see a place for antiosteolytic agents as part of the neoadjuvant therapy in breast cancer,” said lead author Sibylle Loibl, MD, PhD, who is a breast cancer researcher at Goethe (Germany) University. The researchers can’t exclude the possibility of a long-term benefit, and patients will be followed for disease-free and overall survival.

The disappointing result comes after previous studies of denosumab or bisphosphonates as additions to adjuvant therapy reduced metastases and increased survival in breast cancer, prompting optimism that the agents might improve pCR rates and improve survival rates in the neoadjuvant setting.

The failure may be because of the shorter treatment duration, and it’s possible that pCR is not the best endpoint to study for a drug that has long-acting potential, according to Dr. Loibl.

Patients were randomized to 120 mg denosumab every 4 weeks for six cycles or to receive no supplementary treatment. Patients with or without denosumab either received nab-paclitaxel 125 mg/m² weekly for 12 weeks or on days 1 and 8 every 3 weeks, over four cycles (eight total doses), then epirubicin/cyclophosphamide, 90/600 mg/m² (every 2 and 3 weeks, respectively). Patients with triple-negative breast cancer also received carboplatin. Patients with ERBB2-positive breast cancer received the trastuzumab biosimilar ABP980 plus pertuzumab.

The study included 780 patients (1 male), with a median age of 49.0 years. There was no difference in pCR among denosumab recipients and nonrecipients (41.0% versus 42.8%; P = .58). Weekly nab-paclitaxel led to a higher pCR rate than a schedule of days 1 and 8 every 3 weeks (44.9% versus 39.0%; P = .06, significance level of alpha = .10). Among subgroups, there was only a difference in pCR rates among those with TNBC (60.4% versus 50.0%; P = .06). Grade 3-4 toxic effects were similar regardless of denosumab exposure, but nonhematologic grade 3-4 toxicity was higher with weekly nab-paclitaxel (33.7% versus 24.1%; P = .004).

“The overall pCR difference (with nab-paclitaxel as neoadjuvant chemotherapy) seems small, but looking at the data from the GeparSEPTO study we would expect a transformation into a better invasive disease-free survival. Looking specifically into patients with TNBC, there is clear pCR increase by using the weekly regimen. With just over 60%, this is the highest pCR rate reported so far for a chemotherapy-only regimen. I would prefer to use nab-paclitaxel also in early breast cancer and would use the weekly regimen for women with TNBC who are at high risk,” Dr. Loibl said.

The study was limited by an imbalance of tumor subtypes between the treatment groups. The authors wrote that the results should guide further research, but nab-paclitaxel should not currently be viewed as a standard neoadjuvant treatment of breast cancer.

The study was funded by the German Breast Group, Bristol Myers Squibb, and Amgen. Dr. Loibl has served on the advisory boards or given lectures for AbbVie, Amgen, Bayer, Celgene, EirGenix, GSK, Lilly, Merck, Puma, Seagen, AstraZeneca, Daiichi Sankyo, Novartis, Pierre Fabre, Prime/Medscape, Bristol Myers Squibb, Chugai, Ipsen, Roche, and Samsung. She also holds a related patent.

Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.

That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.

“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”

That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.

This situation is hardly unique.

Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.

In a recent perspective in the New England Journal of Medicine, Dr. Dusetzina detailed how subtle variations in people’s cancer type can have major implications for their out-of-pocket drug costs.

The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).

According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.

Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.

In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”

“This is ARBITRARY and INEQUITABLE,” she added.

What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.

Take the drug costs for two similar patients with breast cancer.

Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).

For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.

Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.

This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.

A version of this article first appeared on Medscape.com.

Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.

That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.

“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”

That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.

This situation is hardly unique.

Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.

In a recent perspective in the New England Journal of Medicine, Dr. Dusetzina detailed how subtle variations in people’s cancer type can have major implications for their out-of-pocket drug costs.

The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).

According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.

Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.

In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”

“This is ARBITRARY and INEQUITABLE,” she added.

What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.

Take the drug costs for two similar patients with breast cancer.

Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).

For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.

Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.

This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.

A version of this article first appeared on Medscape.com.

Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.

That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.

“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”

That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.

This situation is hardly unique.

Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.

In a recent perspective in the New England Journal of Medicine, Dr. Dusetzina detailed how subtle variations in people’s cancer type can have major implications for their out-of-pocket drug costs.

The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).

According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.

Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.

In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”

“This is ARBITRARY and INEQUITABLE,” she added.

What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.

Take the drug costs for two similar patients with breast cancer.

Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).

For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.

Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.

This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.

A version of this article first appeared on Medscape.com.

Male breast cancer is linked to infertility, according to a new case-control study from the Institute of Cancer Research in London. The report follows other studies that generally failed to identify a statistically significant association, but the resources of Great Britain’s National Health Service made it possible to achieve greater power than previous efforts.

“It’s a very difficult disease to study because it’s about 100 times rarer than female breast cancer. To do the equivalent study, you either have to make your study 100 times bigger, or think laterally and approach it a different way. (That’s) why we did a case control study where you identify the cases and find controls, rather than wait for men to develop breast cancer,” said Michael Edwin Jones, PhD, the lead author of the study, which was published online in Breast Cancer Research.

The new study found that men who self-reported infertility had a doubled risk of breast cancer, while there was no difference if the fertility was linked to their female partner. Sex hormones are known to play a key role in female breast cancer, and they have a suspected role in male breast cancer as well, though it’s hard to pin down because there is no concentrated source of exposure like hormone therapy or activity from the ovary to cause spiked levels. “It’s more subtle in men, but there’s a reason to think it’s important,” Dr. Jones said.

Although the results hint at a possible role of sex hormones, the research can’t confirm that. Blood draws were taken from participants, but many were conducted after treatment had begun, leading to inconsistent results. Dr. Jones called for more research into biological mechanisms that might explain the increased risk, and suggested that such efforts could lead to a better understanding of breast cancer overall, since the disease in men is not effected by factors like pregnancy and menopause.

Historically, few clinical trials for breast cancer drugs included men, and this has resulted in few approved treatments. However, the impact of breast cancer on men is increasingly being recognized, and most such trials now accept male patients. The Food and Drug Administration has even produced a guidance document for inclusion of men in development of breast cancer drugs, which states that men should be excluded only if there is a clear scientific rationale. When there are too few male participants to draw direct conclusions, it may be possible to extrapolate findings in women to men for FDA approval, provided the mechanism of action suggests that there should be no difference in efficacy.

The Breast Cancer Now study included 1,998 cases and 1,597 controls, who were asked about infertility and whether they had children. Men with male-origin infertility had a higher risk of breast cancer (odds ratio, 2.03; 95% confidence interval [CI], 1.18-3.49), but not men who reported female-origin infertility (OR, 0.86; 95% CI, 0.51-1.45). There was also a heightened risk among men who had not fathered children versus those who had (OR, 1.50; 95% CI, 1.21-1.86).

The association was statistically significant for invasive tumors (OR, 1.96; P = .02), but only a trend was observed for in situ breast cancer (OR, 1.72; P = .39). A possible explanation is that diagnosis of in situ breast cancer is less common than invasive cancer in men, which could have led to the study being underpowered. “Unfortunately, there were too few in-situ breast cancers to allow us to say anything definitive,” said Dr. Jones.

Dr. Jones has no relevant financial disclosures. The study was funded by Breast Cancer Now.

Male breast cancer is linked to infertility, according to a new case-control study from the Institute of Cancer Research in London. The report follows other studies that generally failed to identify a statistically significant association, but the resources of Great Britain’s National Health Service made it possible to achieve greater power than previous efforts.

“It’s a very difficult disease to study because it’s about 100 times rarer than female breast cancer. To do the equivalent study, you either have to make your study 100 times bigger, or think laterally and approach it a different way. (That’s) why we did a case control study where you identify the cases and find controls, rather than wait for men to develop breast cancer,” said Michael Edwin Jones, PhD, the lead author of the study, which was published online in Breast Cancer Research.

The new study found that men who self-reported infertility had a doubled risk of breast cancer, while there was no difference if the fertility was linked to their female partner. Sex hormones are known to play a key role in female breast cancer, and they have a suspected role in male breast cancer as well, though it’s hard to pin down because there is no concentrated source of exposure like hormone therapy or activity from the ovary to cause spiked levels. “It’s more subtle in men, but there’s a reason to think it’s important,” Dr. Jones said.

Although the results hint at a possible role of sex hormones, the research can’t confirm that. Blood draws were taken from participants, but many were conducted after treatment had begun, leading to inconsistent results. Dr. Jones called for more research into biological mechanisms that might explain the increased risk, and suggested that such efforts could lead to a better understanding of breast cancer overall, since the disease in men is not effected by factors like pregnancy and menopause.

Historically, few clinical trials for breast cancer drugs included men, and this has resulted in few approved treatments. However, the impact of breast cancer on men is increasingly being recognized, and most such trials now accept male patients. The Food and Drug Administration has even produced a guidance document for inclusion of men in development of breast cancer drugs, which states that men should be excluded only if there is a clear scientific rationale. When there are too few male participants to draw direct conclusions, it may be possible to extrapolate findings in women to men for FDA approval, provided the mechanism of action suggests that there should be no difference in efficacy.

The Breast Cancer Now study included 1,998 cases and 1,597 controls, who were asked about infertility and whether they had children. Men with male-origin infertility had a higher risk of breast cancer (odds ratio, 2.03; 95% confidence interval [CI], 1.18-3.49), but not men who reported female-origin infertility (OR, 0.86; 95% CI, 0.51-1.45). There was also a heightened risk among men who had not fathered children versus those who had (OR, 1.50; 95% CI, 1.21-1.86).

The association was statistically significant for invasive tumors (OR, 1.96; P = .02), but only a trend was observed for in situ breast cancer (OR, 1.72; P = .39). A possible explanation is that diagnosis of in situ breast cancer is less common than invasive cancer in men, which could have led to the study being underpowered. “Unfortunately, there were too few in-situ breast cancers to allow us to say anything definitive,” said Dr. Jones.

Dr. Jones has no relevant financial disclosures. The study was funded by Breast Cancer Now.

Male breast cancer is linked to infertility, according to a new case-control study from the Institute of Cancer Research in London. The report follows other studies that generally failed to identify a statistically significant association, but the resources of Great Britain’s National Health Service made it possible to achieve greater power than previous efforts.

“It’s a very difficult disease to study because it’s about 100 times rarer than female breast cancer. To do the equivalent study, you either have to make your study 100 times bigger, or think laterally and approach it a different way. (That’s) why we did a case control study where you identify the cases and find controls, rather than wait for men to develop breast cancer,” said Michael Edwin Jones, PhD, the lead author of the study, which was published online in Breast Cancer Research.

The new study found that men who self-reported infertility had a doubled risk of breast cancer, while there was no difference if the fertility was linked to their female partner. Sex hormones are known to play a key role in female breast cancer, and they have a suspected role in male breast cancer as well, though it’s hard to pin down because there is no concentrated source of exposure like hormone therapy or activity from the ovary to cause spiked levels. “It’s more subtle in men, but there’s a reason to think it’s important,” Dr. Jones said.

Although the results hint at a possible role of sex hormones, the research can’t confirm that. Blood draws were taken from participants, but many were conducted after treatment had begun, leading to inconsistent results. Dr. Jones called for more research into biological mechanisms that might explain the increased risk, and suggested that such efforts could lead to a better understanding of breast cancer overall, since the disease in men is not effected by factors like pregnancy and menopause.

Historically, few clinical trials for breast cancer drugs included men, and this has resulted in few approved treatments. However, the impact of breast cancer on men is increasingly being recognized, and most such trials now accept male patients. The Food and Drug Administration has even produced a guidance document for inclusion of men in development of breast cancer drugs, which states that men should be excluded only if there is a clear scientific rationale. When there are too few male participants to draw direct conclusions, it may be possible to extrapolate findings in women to men for FDA approval, provided the mechanism of action suggests that there should be no difference in efficacy.

The Breast Cancer Now study included 1,998 cases and 1,597 controls, who were asked about infertility and whether they had children. Men with male-origin infertility had a higher risk of breast cancer (odds ratio, 2.03; 95% confidence interval [CI], 1.18-3.49), but not men who reported female-origin infertility (OR, 0.86; 95% CI, 0.51-1.45). There was also a heightened risk among men who had not fathered children versus those who had (OR, 1.50; 95% CI, 1.21-1.86).

The association was statistically significant for invasive tumors (OR, 1.96; P = .02), but only a trend was observed for in situ breast cancer (OR, 1.72; P = .39). A possible explanation is that diagnosis of in situ breast cancer is less common than invasive cancer in men, which could have led to the study being underpowered. “Unfortunately, there were too few in-situ breast cancers to allow us to say anything definitive,” said Dr. Jones.

Dr. Jones has no relevant financial disclosures. The study was funded by Breast Cancer Now.

Patients with nonmetastatic triple-negative breast cancer lacking progressive death–ligand 1 expression are less responsive to neoadjuvant chemotherapy and face a poorer prognosis than patients with PD-L1–positive tumors, according to a study presented at ESMO Breast Cancer 2022, a meeting of the European Society for Medical Oncology.

“The newly distinct quadruple negative breast cancer subtype could be considered the breast cancer subtype with the poorest outcome,” wrote the authors, who were led by Loay Kassem, MD, a clinical oncology consultant at Cairo (Egypt) University.

Triple-negative breast cancer (TNBC) accounts for 15%-20% of all breast cancers. It tends to be more aggressive and difficult to treat than other subtypes.

Prior research has shown the expression of PD-L1 in tumors is predictive of immunotherapy response in patients with metastatic TNBC. The checkpoint inhibitor pembrolizumab (Keytruda, Merck) was approved by the Food and Drug Administration in 2021 for high-risk, early-stage, triple-negative breast cancer in combination with neoadjuvant chemotherapy, and then continued as a single treatment after surgery.

To determine whether PD-L1 expression could also predict response to chemotherapy in with nonmetastatic TNBC, the researchers conducted a systematic review and meta-analysis of 19 studies that included a total of 2,319 patients with nonmetastatic TBNC. The team examined whether PD-L1 expression could predict pathological complete response to neoadjuvant chemotherapy. PD-L1–positive TNBC were found to be significantly associated with a higher probability of achieving a pathological complete response with neoadjuvant chemotherapy. Long-term studies have shown that PD-L1 positivity was associated with better disease-free survival and overall survival than PD-L1–negative patients.

The researchers also examined RNA sequence data, which showed that PD-L1 expression was indicative of higher levels of expression of key immune-related genes that mediate response to chemotherapy in TNBC.

Dr. Kassem and colleagues suggest that quadruple-negative breast cancer defined by a lack of PD-L1 expression is a distinct subtype of breast cancer associated with the poorest outcomes. Another quadruple-negative breast cancer – a subtype of TNBC where patients lack expression of the androgen receptor, has also been associated with more aggressive disease and poorer response to treatment.

The authors report no funding or conflicts of interest.

Patients with nonmetastatic triple-negative breast cancer lacking progressive death–ligand 1 expression are less responsive to neoadjuvant chemotherapy and face a poorer prognosis than patients with PD-L1–positive tumors, according to a study presented at ESMO Breast Cancer 2022, a meeting of the European Society for Medical Oncology.

“The newly distinct quadruple negative breast cancer subtype could be considered the breast cancer subtype with the poorest outcome,” wrote the authors, who were led by Loay Kassem, MD, a clinical oncology consultant at Cairo (Egypt) University.

Triple-negative breast cancer (TNBC) accounts for 15%-20% of all breast cancers. It tends to be more aggressive and difficult to treat than other subtypes.

Prior research has shown the expression of PD-L1 in tumors is predictive of immunotherapy response in patients with metastatic TNBC. The checkpoint inhibitor pembrolizumab (Keytruda, Merck) was approved by the Food and Drug Administration in 2021 for high-risk, early-stage, triple-negative breast cancer in combination with neoadjuvant chemotherapy, and then continued as a single treatment after surgery.

To determine whether PD-L1 expression could also predict response to chemotherapy in with nonmetastatic TNBC, the researchers conducted a systematic review and meta-analysis of 19 studies that included a total of 2,319 patients with nonmetastatic TBNC. The team examined whether PD-L1 expression could predict pathological complete response to neoadjuvant chemotherapy. PD-L1–positive TNBC were found to be significantly associated with a higher probability of achieving a pathological complete response with neoadjuvant chemotherapy. Long-term studies have shown that PD-L1 positivity was associated with better disease-free survival and overall survival than PD-L1–negative patients.

The researchers also examined RNA sequence data, which showed that PD-L1 expression was indicative of higher levels of expression of key immune-related genes that mediate response to chemotherapy in TNBC.

Dr. Kassem and colleagues suggest that quadruple-negative breast cancer defined by a lack of PD-L1 expression is a distinct subtype of breast cancer associated with the poorest outcomes. Another quadruple-negative breast cancer – a subtype of TNBC where patients lack expression of the androgen receptor, has also been associated with more aggressive disease and poorer response to treatment.

The authors report no funding or conflicts of interest.

Patients with nonmetastatic triple-negative breast cancer lacking progressive death–ligand 1 expression are less responsive to neoadjuvant chemotherapy and face a poorer prognosis than patients with PD-L1–positive tumors, according to a study presented at ESMO Breast Cancer 2022, a meeting of the European Society for Medical Oncology.

“The newly distinct quadruple negative breast cancer subtype could be considered the breast cancer subtype with the poorest outcome,” wrote the authors, who were led by Loay Kassem, MD, a clinical oncology consultant at Cairo (Egypt) University.

Triple-negative breast cancer (TNBC) accounts for 15%-20% of all breast cancers. It tends to be more aggressive and difficult to treat than other subtypes.

Prior research has shown the expression of PD-L1 in tumors is predictive of immunotherapy response in patients with metastatic TNBC. The checkpoint inhibitor pembrolizumab (Keytruda, Merck) was approved by the Food and Drug Administration in 2021 for high-risk, early-stage, triple-negative breast cancer in combination with neoadjuvant chemotherapy, and then continued as a single treatment after surgery.

To determine whether PD-L1 expression could also predict response to chemotherapy in with nonmetastatic TNBC, the researchers conducted a systematic review and meta-analysis of 19 studies that included a total of 2,319 patients with nonmetastatic TBNC. The team examined whether PD-L1 expression could predict pathological complete response to neoadjuvant chemotherapy. PD-L1–positive TNBC were found to be significantly associated with a higher probability of achieving a pathological complete response with neoadjuvant chemotherapy. Long-term studies have shown that PD-L1 positivity was associated with better disease-free survival and overall survival than PD-L1–negative patients.

The researchers also examined RNA sequence data, which showed that PD-L1 expression was indicative of higher levels of expression of key immune-related genes that mediate response to chemotherapy in TNBC.

Dr. Kassem and colleagues suggest that quadruple-negative breast cancer defined by a lack of PD-L1 expression is a distinct subtype of breast cancer associated with the poorest outcomes. Another quadruple-negative breast cancer – a subtype of TNBC where patients lack expression of the androgen receptor, has also been associated with more aggressive disease and poorer response to treatment.

The authors report no funding or conflicts of interest.

Mastectomies among younger women with nonmetastatic invasive breast cancer may not always be necessary, according to a new study that shows survival outcomes are similar to those of women who had a lumpectomy.

The results come as an increasing number of women under 40 choose mastectomy. “A lot of times, there’s this assumption that removal of the entire breast is going to prevent cancer from returning in that breast. That makes complete sense, it’s intuitive, so I think a lot of patients are surprised to find that less extensive surgery provides the same overall survival as a really extensive surgery,” said Christine Pestana, MD, a fellow in breast surgical oncology with the Atrium Health Levine Cancer Institute, Charlotte, N.C. Dr. Pestana presented the study at the annual meeting of the American Society of Breast Surgeons earlier this year.

In fact, it has been well-demonstrated among women over age 50 with breast cancer that lumpectomy and mastectomy result in similar outcomes, but efforts to show similar efficacy by analyzing data from randomized trials have been limited by small numbers of women under 40, said the study’s lead author Lejla Hadzikadic-Gusic, MD, who is codirector of the Sandra Levine Young Women’s Breast Cancer Program at Atrium Health. “We’ve done a lot of research since the 1970s to be able to keep a woman’s breasts and just treat her for breast cancer. It’s nice to be able to say the same thing for younger women,” said Dr. Hadzikadic-Gusic, in an interview.

The researchers drew from the Young Women’s Database from the Levine Cancer Institute. The analysis included data from nearly 600 women treated between 2010 and 2018.

The increasing frequency of mastectomies in younger women may be traceable, in part, to high-profile cases of celebrities who have had mastectomies after an early breast cancer diagnosis, with Angelina Jolie being among the most known of examples. But Ms. Jolie had the procedure proactively without a cancer diagnosis because she carried the BRCA1 mutation, which increases breast cancer risk. That information was often lost in press coverage, which can lead to confusion among young women with breast cancer, according to Dr. Hadzikadic-Gusic. “What we’re trying to do is have this data help us educate our patients,” she said.

It’s also important for physicians to help guide patients through these decisions, and family history is a key factor. Dr. Pestana encourages primary care providers to explore family history to help understand cancer risks. “It’s not just breast cancer. It’s also ovarian cancer, colon cancer, prostate cancer. Those all have associations with different genetic mutations. If we start asking those questions, we may be able to identify patients who potentially could have that mutation, refer them to a geneticist, have them tested,” she said.

All of the 591 patients in the study were under age 40, with a median age of 37, and the median follow-up was 67 months. Twelve percent of patients died; 53.3% of patients were HR+/HER2–, 20.8% were HR+/HER2+, 19.3% were triple negative, and 6.6% were HR–/HER2+. There was no association between type of surgery and mortality.

The study was funded by the Levine Family Cancer Institute. Dr. Pestana and Dr. Hadzikadic-Gusic have no relevant financial disclosures.

Mastectomies among younger women with nonmetastatic invasive breast cancer may not always be necessary, according to a new study that shows survival outcomes are similar to those of women who had a lumpectomy.

The results come as an increasing number of women under 40 choose mastectomy. “A lot of times, there’s this assumption that removal of the entire breast is going to prevent cancer from returning in that breast. That makes complete sense, it’s intuitive, so I think a lot of patients are surprised to find that less extensive surgery provides the same overall survival as a really extensive surgery,” said Christine Pestana, MD, a fellow in breast surgical oncology with the Atrium Health Levine Cancer Institute, Charlotte, N.C. Dr. Pestana presented the study at the annual meeting of the American Society of Breast Surgeons earlier this year.

In fact, it has been well-demonstrated among women over age 50 with breast cancer that lumpectomy and mastectomy result in similar outcomes, but efforts to show similar efficacy by analyzing data from randomized trials have been limited by small numbers of women under 40, said the study’s lead author Lejla Hadzikadic-Gusic, MD, who is codirector of the Sandra Levine Young Women’s Breast Cancer Program at Atrium Health. “We’ve done a lot of research since the 1970s to be able to keep a woman’s breasts and just treat her for breast cancer. It’s nice to be able to say the same thing for younger women,” said Dr. Hadzikadic-Gusic, in an interview.

The researchers drew from the Young Women’s Database from the Levine Cancer Institute. The analysis included data from nearly 600 women treated between 2010 and 2018.

The increasing frequency of mastectomies in younger women may be traceable, in part, to high-profile cases of celebrities who have had mastectomies after an early breast cancer diagnosis, with Angelina Jolie being among the most known of examples. But Ms. Jolie had the procedure proactively without a cancer diagnosis because she carried the BRCA1 mutation, which increases breast cancer risk. That information was often lost in press coverage, which can lead to confusion among young women with breast cancer, according to Dr. Hadzikadic-Gusic. “What we’re trying to do is have this data help us educate our patients,” she said.

It’s also important for physicians to help guide patients through these decisions, and family history is a key factor. Dr. Pestana encourages primary care providers to explore family history to help understand cancer risks. “It’s not just breast cancer. It’s also ovarian cancer, colon cancer, prostate cancer. Those all have associations with different genetic mutations. If we start asking those questions, we may be able to identify patients who potentially could have that mutation, refer them to a geneticist, have them tested,” she said.

All of the 591 patients in the study were under age 40, with a median age of 37, and the median follow-up was 67 months. Twelve percent of patients died; 53.3% of patients were HR+/HER2–, 20.8% were HR+/HER2+, 19.3% were triple negative, and 6.6% were HR–/HER2+. There was no association between type of surgery and mortality.

The study was funded by the Levine Family Cancer Institute. Dr. Pestana and Dr. Hadzikadic-Gusic have no relevant financial disclosures.

Mastectomies among younger women with nonmetastatic invasive breast cancer may not always be necessary, according to a new study that shows survival outcomes are similar to those of women who had a lumpectomy.

The results come as an increasing number of women under 40 choose mastectomy. “A lot of times, there’s this assumption that removal of the entire breast is going to prevent cancer from returning in that breast. That makes complete sense, it’s intuitive, so I think a lot of patients are surprised to find that less extensive surgery provides the same overall survival as a really extensive surgery,” said Christine Pestana, MD, a fellow in breast surgical oncology with the Atrium Health Levine Cancer Institute, Charlotte, N.C. Dr. Pestana presented the study at the annual meeting of the American Society of Breast Surgeons earlier this year.

In fact, it has been well-demonstrated among women over age 50 with breast cancer that lumpectomy and mastectomy result in similar outcomes, but efforts to show similar efficacy by analyzing data from randomized trials have been limited by small numbers of women under 40, said the study’s lead author Lejla Hadzikadic-Gusic, MD, who is codirector of the Sandra Levine Young Women’s Breast Cancer Program at Atrium Health. “We’ve done a lot of research since the 1970s to be able to keep a woman’s breasts and just treat her for breast cancer. It’s nice to be able to say the same thing for younger women,” said Dr. Hadzikadic-Gusic, in an interview.

The researchers drew from the Young Women’s Database from the Levine Cancer Institute. The analysis included data from nearly 600 women treated between 2010 and 2018.

The increasing frequency of mastectomies in younger women may be traceable, in part, to high-profile cases of celebrities who have had mastectomies after an early breast cancer diagnosis, with Angelina Jolie being among the most known of examples. But Ms. Jolie had the procedure proactively without a cancer diagnosis because she carried the BRCA1 mutation, which increases breast cancer risk. That information was often lost in press coverage, which can lead to confusion among young women with breast cancer, according to Dr. Hadzikadic-Gusic. “What we’re trying to do is have this data help us educate our patients,” she said.

It’s also important for physicians to help guide patients through these decisions, and family history is a key factor. Dr. Pestana encourages primary care providers to explore family history to help understand cancer risks. “It’s not just breast cancer. It’s also ovarian cancer, colon cancer, prostate cancer. Those all have associations with different genetic mutations. If we start asking those questions, we may be able to identify patients who potentially could have that mutation, refer them to a geneticist, have them tested,” she said.

All of the 591 patients in the study were under age 40, with a median age of 37, and the median follow-up was 67 months. Twelve percent of patients died; 53.3% of patients were HR+/HER2–, 20.8% were HR+/HER2+, 19.3% were triple negative, and 6.6% were HR–/HER2+. There was no association between type of surgery and mortality.

The study was funded by the Levine Family Cancer Institute. Dr. Pestana and Dr. Hadzikadic-Gusic have no relevant financial disclosures.

A study presented at ESMO Breast Cancer 2022 documents a “significant long-term benefit” among women with breast cancer who were treated with tamoxifen.

The study was a secondary analysis of women with estrogen receptor (ER)-positive HER2-negative breast cancer who were treated between 1976 and 1996 in Sweden.

“Our findings suggest a significant long-term tamoxifen treatment benefit among patients with larger tumors, lymph node-negative tumors, PR-positive tumors, and Ki-67 low tumors,” according to Huma Dar, a doctoral candidate at Karolinska Institute, Stockholm, who authored the study.

The analysis found that patients with tumor size T1c, grade 2, lymph node-negative, PR-positive, and Ki-67-low tumors significantly benefited from treatment with tamoxifen for 20 years. And, for patients with tumor size T2-3, benefited significantly after 10 years of treatment with tamoxifen.

It is known that breast cancer patients with ER-positive tumors have a greater risk of distant recurrence – cancer spreading to tissues and organs far from the original tumor site. The selective estrogen receptor modulator tamoxifen, when used as an adjuvant therapy, has been shown to reduce the risk of tumor recurrence and increase survival in patients with ER-positive breast cancer, but not all patients benefit from this therapy.

To examine the long-term benefit of tamoxifen, Ms. Dar and colleagues analyzed data from randomized clinical trials of tamoxifen that took place in Stockholm between 1976 and 1997. The study included 1,242 patients with ER-positive/HER2-negative breast cancer and included a 20-year follow-up. Researchers looked at the relationship between tumor characteristics – including size, grade, lymph node status, the presence of progesterone receptor (PR), and levels of Ki-67, a protein linked with cell proliferation – and patient outcomes. 

In a related study published last year in JAMA Network Open, Ms. Dar and colleagues examined the long-term effects of tamoxifen in patients with low risk, postmenopausal, and lymph-node negative cancer. They found that patients with larger tumors, lower tumor grade and PR-positive tumors appeared to significantly benefit from tamoxifen treatment for up to 25 years. The team has since extended that work by looking at pre- and postmenopausal as well as low- and high-risk patients, Ms. Dar said. 

“We believe that our findings together with other study findings are important to understand the lifetime risk for patients diagnosed with breast cancer,” Ms. Dar said. “One potential clinical implication is related to tamoxifen benefit, which in our study we don’t see for patients with the smallest tumors.” She said that more studies are needed to confirm this result.

A limitation of this study is that clinical recommendations for disease management and treatment have changed since the initiation of the clinical trials. “The STO-trials were performed before aromatase inhibitors or ovarian function suppression became one of the recommended treatment options for ER-positive breast cancer, and when the duration of tamoxifen therapy was shorter than current recommendations,” Ms. Dar said.

The study was funded by the Swedish Research Council, Swedish Research Council for Health, Working life and Welfare, The Gösta Milton Donation Fund, and Swedish Cancer Society. The authors had no relevant disclosures.

A study presented at ESMO Breast Cancer 2022 documents a “significant long-term benefit” among women with breast cancer who were treated with tamoxifen.

The study was a secondary analysis of women with estrogen receptor (ER)-positive HER2-negative breast cancer who were treated between 1976 and 1996 in Sweden.

“Our findings suggest a significant long-term tamoxifen treatment benefit among patients with larger tumors, lymph node-negative tumors, PR-positive tumors, and Ki-67 low tumors,” according to Huma Dar, a doctoral candidate at Karolinska Institute, Stockholm, who authored the study.

The analysis found that patients with tumor size T1c, grade 2, lymph node-negative, PR-positive, and Ki-67-low tumors significantly benefited from treatment with tamoxifen for 20 years. And, for patients with tumor size T2-3, benefited significantly after 10 years of treatment with tamoxifen.

It is known that breast cancer patients with ER-positive tumors have a greater risk of distant recurrence – cancer spreading to tissues and organs far from the original tumor site. The selective estrogen receptor modulator tamoxifen, when used as an adjuvant therapy, has been shown to reduce the risk of tumor recurrence and increase survival in patients with ER-positive breast cancer, but not all patients benefit from this therapy.

To examine the long-term benefit of tamoxifen, Ms. Dar and colleagues analyzed data from randomized clinical trials of tamoxifen that took place in Stockholm between 1976 and 1997. The study included 1,242 patients with ER-positive/HER2-negative breast cancer and included a 20-year follow-up. Researchers looked at the relationship between tumor characteristics – including size, grade, lymph node status, the presence of progesterone receptor (PR), and levels of Ki-67, a protein linked with cell proliferation – and patient outcomes. 

In a related study published last year in JAMA Network Open, Ms. Dar and colleagues examined the long-term effects of tamoxifen in patients with low risk, postmenopausal, and lymph-node negative cancer. They found that patients with larger tumors, lower tumor grade and PR-positive tumors appeared to significantly benefit from tamoxifen treatment for up to 25 years. The team has since extended that work by looking at pre- and postmenopausal as well as low- and high-risk patients, Ms. Dar said. 

“We believe that our findings together with other study findings are important to understand the lifetime risk for patients diagnosed with breast cancer,” Ms. Dar said. “One potential clinical implication is related to tamoxifen benefit, which in our study we don’t see for patients with the smallest tumors.” She said that more studies are needed to confirm this result.

A limitation of this study is that clinical recommendations for disease management and treatment have changed since the initiation of the clinical trials. “The STO-trials were performed before aromatase inhibitors or ovarian function suppression became one of the recommended treatment options for ER-positive breast cancer, and when the duration of tamoxifen therapy was shorter than current recommendations,” Ms. Dar said.

The study was funded by the Swedish Research Council, Swedish Research Council for Health, Working life and Welfare, The Gösta Milton Donation Fund, and Swedish Cancer Society. The authors had no relevant disclosures.

A study presented at ESMO Breast Cancer 2022 documents a “significant long-term benefit” among women with breast cancer who were treated with tamoxifen.

The study was a secondary analysis of women with estrogen receptor (ER)-positive HER2-negative breast cancer who were treated between 1976 and 1996 in Sweden.

“Our findings suggest a significant long-term tamoxifen treatment benefit among patients with larger tumors, lymph node-negative tumors, PR-positive tumors, and Ki-67 low tumors,” according to Huma Dar, a doctoral candidate at Karolinska Institute, Stockholm, who authored the study.

The analysis found that patients with tumor size T1c, grade 2, lymph node-negative, PR-positive, and Ki-67-low tumors significantly benefited from treatment with tamoxifen for 20 years. And, for patients with tumor size T2-3, benefited significantly after 10 years of treatment with tamoxifen.

It is known that breast cancer patients with ER-positive tumors have a greater risk of distant recurrence – cancer spreading to tissues and organs far from the original tumor site. The selective estrogen receptor modulator tamoxifen, when used as an adjuvant therapy, has been shown to reduce the risk of tumor recurrence and increase survival in patients with ER-positive breast cancer, but not all patients benefit from this therapy.

To examine the long-term benefit of tamoxifen, Ms. Dar and colleagues analyzed data from randomized clinical trials of tamoxifen that took place in Stockholm between 1976 and 1997. The study included 1,242 patients with ER-positive/HER2-negative breast cancer and included a 20-year follow-up. Researchers looked at the relationship between tumor characteristics – including size, grade, lymph node status, the presence of progesterone receptor (PR), and levels of Ki-67, a protein linked with cell proliferation – and patient outcomes. 

In a related study published last year in JAMA Network Open, Ms. Dar and colleagues examined the long-term effects of tamoxifen in patients with low risk, postmenopausal, and lymph-node negative cancer. They found that patients with larger tumors, lower tumor grade and PR-positive tumors appeared to significantly benefit from tamoxifen treatment for up to 25 years. The team has since extended that work by looking at pre- and postmenopausal as well as low- and high-risk patients, Ms. Dar said. 

“We believe that our findings together with other study findings are important to understand the lifetime risk for patients diagnosed with breast cancer,” Ms. Dar said. “One potential clinical implication is related to tamoxifen benefit, which in our study we don’t see for patients with the smallest tumors.” She said that more studies are needed to confirm this result.

A limitation of this study is that clinical recommendations for disease management and treatment have changed since the initiation of the clinical trials. “The STO-trials were performed before aromatase inhibitors or ovarian function suppression became one of the recommended treatment options for ER-positive breast cancer, and when the duration of tamoxifen therapy was shorter than current recommendations,” Ms. Dar said.

The study was funded by the Swedish Research Council, Swedish Research Council for Health, Working life and Welfare, The Gösta Milton Donation Fund, and Swedish Cancer Society. The authors had no relevant disclosures.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

In an updated clinical practice guideline, the American Society of Clinical Oncology has named the Breast Cancer Index (BCI) as the only genomic test that should be used to guide extended endocrine therapy decisions for women with early-stage, hormone receptor–positive breast cancer. The update applies to women who are node negative or have one to three positive nodes treated with 5 years of endocrine therapy and no sign of recurrence.

The update was published in the Journal of Clinical Oncology. It also gives more specific details on how to apply other, previously recommended, genomic tests to guide treatment choices.

More than half of breast cancer deaths occur after 5 years of tamoxifen therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP)- B14 trial, published in 2001, showed no benefit to extending tamoxifen therapy to 10 years, but other studies have produced mixed results.

Extended endocrine therapy may reduce the risk of recurrence, but significant side effects can impact quality of life, including osteoporosis, bone fractures, and joint pain. The uncertain benefits of extended endocrine therapy, combined with its side effects and impact on quality of life, has generated interest in genomic tests to identify patients most likely to benefit.

The BCI analyzes 11 genes from the tumor and delivers two results: the likelihood of recurrence 5-10 years after diagnosis, and whether a total of 10 years of endocrine therapy are likely to provide a survival benefit.

The 21-gene prognostic and predictive assay Oncotype DX Breast Recurrence Score, the 70-gene signature test Mammaprint, the 12-gene risk score EndoPredict, levels of Ki67 expression, and immunohistochemistry are also recommended for guiding decisions on endocrine therapy. The update included additional guidance on specific situations that each can be used. However, their usefulness for predicting recurrence at 5-10 years is unproven.

“The clinical decision to either extend or end adjuvant endocrine therapy after 5 years is a challenging decision for healthcare providers and their patients,” Mark Pegram, MD, said in a press release. He is chief medical consultant for breast oncology at Biotheranostics, a subsidiary of Hologic. “There is an extensive body of clinical evidence consistently proving the utility of BCI, and its addition to major oncology clinical guidelines like those from ASCO further underscores the test’s potential in clinical decision-making regarding extended adjuvant endocrine therapy.”

The practice update cited five previous studies showing the ability of BCI to predict benefit from extending endocrine therapy: From 5 years of tamoxifen to 5 more years of tamoxifen; from 5 years of tamoxifen to 5 years of an aromatase inhibitor, and from 5 years of an AI to another 5 years of a drug from the same class. Most of the trials included patients who were node negative or had one to three positive nodes, so there is limited evidence supporting BCI in patients with more than three positive lymph nodes. The recommendation also applies only to postmenopausal women, as the trials included fewer premenopausal and perimenopausal women.

Several of the guideline authors reported conflicts of interest with numerous sources.

In an updated clinical practice guideline, the American Society of Clinical Oncology has named the Breast Cancer Index (BCI) as the only genomic test that should be used to guide extended endocrine therapy decisions for women with early-stage, hormone receptor–positive breast cancer. The update applies to women who are node negative or have one to three positive nodes treated with 5 years of endocrine therapy and no sign of recurrence.

The update was published in the Journal of Clinical Oncology. It also gives more specific details on how to apply other, previously recommended, genomic tests to guide treatment choices.

More than half of breast cancer deaths occur after 5 years of tamoxifen therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP)- B14 trial, published in 2001, showed no benefit to extending tamoxifen therapy to 10 years, but other studies have produced mixed results.

Extended endocrine therapy may reduce the risk of recurrence, but significant side effects can impact quality of life, including osteoporosis, bone fractures, and joint pain. The uncertain benefits of extended endocrine therapy, combined with its side effects and impact on quality of life, has generated interest in genomic tests to identify patients most likely to benefit.

The BCI analyzes 11 genes from the tumor and delivers two results: the likelihood of recurrence 5-10 years after diagnosis, and whether a total of 10 years of endocrine therapy are likely to provide a survival benefit.

The 21-gene prognostic and predictive assay Oncotype DX Breast Recurrence Score, the 70-gene signature test Mammaprint, the 12-gene risk score EndoPredict, levels of Ki67 expression, and immunohistochemistry are also recommended for guiding decisions on endocrine therapy. The update included additional guidance on specific situations that each can be used. However, their usefulness for predicting recurrence at 5-10 years is unproven.

“The clinical decision to either extend or end adjuvant endocrine therapy after 5 years is a challenging decision for healthcare providers and their patients,” Mark Pegram, MD, said in a press release. He is chief medical consultant for breast oncology at Biotheranostics, a subsidiary of Hologic. “There is an extensive body of clinical evidence consistently proving the utility of BCI, and its addition to major oncology clinical guidelines like those from ASCO further underscores the test’s potential in clinical decision-making regarding extended adjuvant endocrine therapy.”

The practice update cited five previous studies showing the ability of BCI to predict benefit from extending endocrine therapy: From 5 years of tamoxifen to 5 more years of tamoxifen; from 5 years of tamoxifen to 5 years of an aromatase inhibitor, and from 5 years of an AI to another 5 years of a drug from the same class. Most of the trials included patients who were node negative or had one to three positive nodes, so there is limited evidence supporting BCI in patients with more than three positive lymph nodes. The recommendation also applies only to postmenopausal women, as the trials included fewer premenopausal and perimenopausal women.

Several of the guideline authors reported conflicts of interest with numerous sources.

In an updated clinical practice guideline, the American Society of Clinical Oncology has named the Breast Cancer Index (BCI) as the only genomic test that should be used to guide extended endocrine therapy decisions for women with early-stage, hormone receptor–positive breast cancer. The update applies to women who are node negative or have one to three positive nodes treated with 5 years of endocrine therapy and no sign of recurrence.

The update was published in the Journal of Clinical Oncology. It also gives more specific details on how to apply other, previously recommended, genomic tests to guide treatment choices.

More than half of breast cancer deaths occur after 5 years of tamoxifen therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP)- B14 trial, published in 2001, showed no benefit to extending tamoxifen therapy to 10 years, but other studies have produced mixed results.

Extended endocrine therapy may reduce the risk of recurrence, but significant side effects can impact quality of life, including osteoporosis, bone fractures, and joint pain. The uncertain benefits of extended endocrine therapy, combined with its side effects and impact on quality of life, has generated interest in genomic tests to identify patients most likely to benefit.

The BCI analyzes 11 genes from the tumor and delivers two results: the likelihood of recurrence 5-10 years after diagnosis, and whether a total of 10 years of endocrine therapy are likely to provide a survival benefit.

The 21-gene prognostic and predictive assay Oncotype DX Breast Recurrence Score, the 70-gene signature test Mammaprint, the 12-gene risk score EndoPredict, levels of Ki67 expression, and immunohistochemistry are also recommended for guiding decisions on endocrine therapy. The update included additional guidance on specific situations that each can be used. However, their usefulness for predicting recurrence at 5-10 years is unproven.

“The clinical decision to either extend or end adjuvant endocrine therapy after 5 years is a challenging decision for healthcare providers and their patients,” Mark Pegram, MD, said in a press release. He is chief medical consultant for breast oncology at Biotheranostics, a subsidiary of Hologic. “There is an extensive body of clinical evidence consistently proving the utility of BCI, and its addition to major oncology clinical guidelines like those from ASCO further underscores the test’s potential in clinical decision-making regarding extended adjuvant endocrine therapy.”

The practice update cited five previous studies showing the ability of BCI to predict benefit from extending endocrine therapy: From 5 years of tamoxifen to 5 more years of tamoxifen; from 5 years of tamoxifen to 5 years of an aromatase inhibitor, and from 5 years of an AI to another 5 years of a drug from the same class. Most of the trials included patients who were node negative or had one to three positive nodes, so there is limited evidence supporting BCI in patients with more than three positive lymph nodes. The recommendation also applies only to postmenopausal women, as the trials included fewer premenopausal and perimenopausal women.

Several of the guideline authors reported conflicts of interest with numerous sources.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

More than one in seven patients with breast cancer saw their financial status deteriorate within the first years after their diagnosis, a new study found. Factors like disease severity and treatment type didn’t seem to have an impact on financial status.

The findings, presented at the annual meeting of the American Association for Cancer Research, were unexpected. “We were surprised that we did not find that patients who received more aggressive therapies were more likely to experience worsening financial concerns,” said corresponding author and medical oncologist Kathryn J. Ruddy, MD, of the Mayo Clinici in Rochester, Minn.

The study was undertaken to understand the financial stress facing patients with breast cancer. The question was whether individual or disease factors, or both, were at play.

The study is based on results from the Mayo Clinic Breast Disease Registry, a prospective cohort of patient who were at Mayo Clinic Rochester. Participants answered questions about their finances at baseline and then again at annual follow-ups.

Researchers examined survey findings from 1,957 patients (mean age 58.5, 99.1% female, 95.4% White, 54.9% bachelor degree or higher) who answered questions at least twice from 2015-2020. The average time between diagnosis and the most recent follow-up was 25.6 months.

Of the 1,957 patients, 357 (18.2%) said their finances deteriorated as measured by a 1 point or higher decline on a 10-point scale.

There was no statistically significant link between deteriorating finances and age, race, employment status, stage of cancer at diagnosis, type of cancer, or treatment type. There was a slight link between deteriorating finances and reporting that they were in the category of “pay bills, no money for special things” near diagnosis.

Other research has suggested that breast cancer may not disrupt finances to a large extent, at least early on. Earlier in 2022, Stanford (Calif.) University researchers reported the results of a survey of 273 breast and gynecologic cancer patients who were surveyed about their finances at a mean of 3.4 years after diagnosis. While one-third said their cancer caused career changes, the study described overall financial toxicity as mild.

In regard to limitations, the subject population of the new study is overwhelmingly White, and the finances were self-reported by those who participated in the survey. Also, “because our participants were recruited at a tertiary medical center, there were relatively financially secure at baseline,” Dr. Ruddy said. “More financial hardship would be expected in a more financially diverse population.”

In an interview, Cathy Bradley, PhD, associate dean for research at the University of Colorado at Denver and deputy director of the University of Colorado Cancer Center, both in Aurora, praised the study as “an important start toward assessing financial burden in the clinic. Having more universal assessments in the clinic would remove stigma.”

She cautioned about interpreting a seemingly low number of patients whose financial situation worsened. “This was for a single site where there is a high rate of health insurance either through Medicare or Medicaid. There may be some selection bias as well given that Mayo may attract a wealthier patient population. Most women completed treatment and may not have been on long-term therapies.”

Moving forward, Dr. Ruddy said, “we hope to study cost of oncologic care in more geographically and financially diverse populations with breast cancer and other cancers.”

The study was funded by the Breast Cancer Research Foundation and National Cancer Institute. The study authors and Dr. Ruddy report no relevant disclosures.

More than one in seven patients with breast cancer saw their financial status deteriorate within the first years after their diagnosis, a new study found. Factors like disease severity and treatment type didn’t seem to have an impact on financial status.

The findings, presented at the annual meeting of the American Association for Cancer Research, were unexpected. “We were surprised that we did not find that patients who received more aggressive therapies were more likely to experience worsening financial concerns,” said corresponding author and medical oncologist Kathryn J. Ruddy, MD, of the Mayo Clinici in Rochester, Minn.

The study was undertaken to understand the financial stress facing patients with breast cancer. The question was whether individual or disease factors, or both, were at play.

The study is based on results from the Mayo Clinic Breast Disease Registry, a prospective cohort of patient who were at Mayo Clinic Rochester. Participants answered questions about their finances at baseline and then again at annual follow-ups.

Researchers examined survey findings from 1,957 patients (mean age 58.5, 99.1% female, 95.4% White, 54.9% bachelor degree or higher) who answered questions at least twice from 2015-2020. The average time between diagnosis and the most recent follow-up was 25.6 months.

Of the 1,957 patients, 357 (18.2%) said their finances deteriorated as measured by a 1 point or higher decline on a 10-point scale.

There was no statistically significant link between deteriorating finances and age, race, employment status, stage of cancer at diagnosis, type of cancer, or treatment type. There was a slight link between deteriorating finances and reporting that they were in the category of “pay bills, no money for special things” near diagnosis.

Other research has suggested that breast cancer may not disrupt finances to a large extent, at least early on. Earlier in 2022, Stanford (Calif.) University researchers reported the results of a survey of 273 breast and gynecologic cancer patients who were surveyed about their finances at a mean of 3.4 years after diagnosis. While one-third said their cancer caused career changes, the study described overall financial toxicity as mild.

In regard to limitations, the subject population of the new study is overwhelmingly White, and the finances were self-reported by those who participated in the survey. Also, “because our participants were recruited at a tertiary medical center, there were relatively financially secure at baseline,” Dr. Ruddy said. “More financial hardship would be expected in a more financially diverse population.”

In an interview, Cathy Bradley, PhD, associate dean for research at the University of Colorado at Denver and deputy director of the University of Colorado Cancer Center, both in Aurora, praised the study as “an important start toward assessing financial burden in the clinic. Having more universal assessments in the clinic would remove stigma.”

She cautioned about interpreting a seemingly low number of patients whose financial situation worsened. “This was for a single site where there is a high rate of health insurance either through Medicare or Medicaid. There may be some selection bias as well given that Mayo may attract a wealthier patient population. Most women completed treatment and may not have been on long-term therapies.”

Moving forward, Dr. Ruddy said, “we hope to study cost of oncologic care in more geographically and financially diverse populations with breast cancer and other cancers.”

The study was funded by the Breast Cancer Research Foundation and National Cancer Institute. The study authors and Dr. Ruddy report no relevant disclosures.

More than one in seven patients with breast cancer saw their financial status deteriorate within the first years after their diagnosis, a new study found. Factors like disease severity and treatment type didn’t seem to have an impact on financial status.

The findings, presented at the annual meeting of the American Association for Cancer Research, were unexpected. “We were surprised that we did not find that patients who received more aggressive therapies were more likely to experience worsening financial concerns,” said corresponding author and medical oncologist Kathryn J. Ruddy, MD, of the Mayo Clinici in Rochester, Minn.

The study was undertaken to understand the financial stress facing patients with breast cancer. The question was whether individual or disease factors, or both, were at play.

The study is based on results from the Mayo Clinic Breast Disease Registry, a prospective cohort of patient who were at Mayo Clinic Rochester. Participants answered questions about their finances at baseline and then again at annual follow-ups.

Researchers examined survey findings from 1,957 patients (mean age 58.5, 99.1% female, 95.4% White, 54.9% bachelor degree or higher) who answered questions at least twice from 2015-2020. The average time between diagnosis and the most recent follow-up was 25.6 months.

Of the 1,957 patients, 357 (18.2%) said their finances deteriorated as measured by a 1 point or higher decline on a 10-point scale.

There was no statistically significant link between deteriorating finances and age, race, employment status, stage of cancer at diagnosis, type of cancer, or treatment type. There was a slight link between deteriorating finances and reporting that they were in the category of “pay bills, no money for special things” near diagnosis.

Other research has suggested that breast cancer may not disrupt finances to a large extent, at least early on. Earlier in 2022, Stanford (Calif.) University researchers reported the results of a survey of 273 breast and gynecologic cancer patients who were surveyed about their finances at a mean of 3.4 years after diagnosis. While one-third said their cancer caused career changes, the study described overall financial toxicity as mild.

In regard to limitations, the subject population of the new study is overwhelmingly White, and the finances were self-reported by those who participated in the survey. Also, “because our participants were recruited at a tertiary medical center, there were relatively financially secure at baseline,” Dr. Ruddy said. “More financial hardship would be expected in a more financially diverse population.”

In an interview, Cathy Bradley, PhD, associate dean for research at the University of Colorado at Denver and deputy director of the University of Colorado Cancer Center, both in Aurora, praised the study as “an important start toward assessing financial burden in the clinic. Having more universal assessments in the clinic would remove stigma.”

She cautioned about interpreting a seemingly low number of patients whose financial situation worsened. “This was for a single site where there is a high rate of health insurance either through Medicare or Medicaid. There may be some selection bias as well given that Mayo may attract a wealthier patient population. Most women completed treatment and may not have been on long-term therapies.”

Moving forward, Dr. Ruddy said, “we hope to study cost of oncologic care in more geographically and financially diverse populations with breast cancer and other cancers.”

The study was funded by the Breast Cancer Research Foundation and National Cancer Institute. The study authors and Dr. Ruddy report no relevant disclosures.