NCCN Annual Conference 2016

HOLLYWOOD, FLA. – No huge surprises here, but newly revised National Comprehensive Cancer Network guidelines for locoregional therapy of breast cancer help clarify the optimal use of adjuvant radiation.

For example, updates to the pages on principles of radiation therapy in invasive breast cancer contain new information on optimal dosing, fractionation, treatment planning, and techniques for minimizing radiation of surrounding normal tissues, noted Dr. Kilian E. Salerno, director of breast radiation and soft tissue/melanoma radiation at the Roswell Park Cancer Institute in Buffalo, New York.

“There are a number of treatment options, many more now than ever before,” she said at the annual conference of the National Comprehensive Cancer Network.

The guidelines emphasize the importance of individualized radiation therapy planning and delivery. A CT-based treatment plan can help clinicians choose target volumes and identify adjacent organs and tissues that may be at risk for radiation spill.

Recommended options for reducing radiation doses to adjacent tissues include deep breath holds and prone positioning so that the treated breast hangs down, helping to isolate it from the heart and lungs.

Whole breast irradiation

Whole breast irradiation is the standard for radiation therapy of early breast cancer following breast-conserving surgery, although partial breast irradiation, typically of lumpectomy cavities, is also commonly performed, Dr. Salerno said.

Boost radiation in conjunction with breast conserving therapy can be delivered via en face electron fields, photons, or brachytherapy; boost dosing to chest wall scar is usually treated with photons or electrons, the guidelines note.

The guidelines recommend weekly imaging to ensure that daily treatment setup is consistent, but caution against routine use of daily imaging.

For whole breast irradiation, the guidelines recommend either doses of 46-50 Gy divided into 23-25 fractions (conventional fractionation), or, preferably, hypofractionated radiation delivered in doses of 40-42.5 Gy over 15-16 fractions, with all doses given 5 days per week. Patients at higher risk for recurrence should receive boost doses to the tumor bed, typically at doses of 10-16 Gy delivered in 4-8 fractions.

The guidelines now favor hypofractionation based on long-term results from clinical trials conducted in Ontario, Canada, and in London.

In the Canadian trial (N Engl J Med. 2010;362:513-20), patients were treated with whole-breast irradiation at doses of 42.5 Gy in 16 fractions, with no boost dose.

In the Standardisation of Breast Radiotherapy B (START B) trial (Lancet Oncol. 14;11:1086-94), in London, patients received 40 Gy in 15 fractions without a boost dose.

Both trials showed that hypofractionation was associated with disease outcomes that were equivalent or better to those seen with conventional fractionation schedules, as well as equivalent or better cosmesis and adverse event profiles, Dr. Salerno said.

“This is for whole breast radiation; it is not to be routinely used in the post-mastectomy setting or when you’re treating regional nodes,” she said.

Accelerated partial breast irradiation

For accelerated partial breast irradiation (APBI), the guidelines recommend a hypofractionated schedule of 34 Gy divided into 10 fractions delivered twice daily for 5 days for brachytherapy, or 38.5 Gy in 10 twice daily fractions with external beam therapy to the tumor bed.

The NCCN guidelines for APBI are based on the American Society of Radiation Oncology (ASTRO) consensus statement for APBI. An updated statement is planned for 2017.

Omit radiation?

Results from the CALGB 9343 trial and other studies suggest that in selected women with lower risk for recurrence, radiation can be omitted without compromising survival. These include women aged 70 or older with small primary breast cancers, negative nodes, negative surgical margins, and hormone-receptor-positive disease who are treated with breast conserving surgery and go on to tamoxifen maintenance.

Post-mastectomy radiation

Following total mastectomy with surgical axillary staging, with our without reconstruction, the guidelines recommend specific steps based on the number of nodes involved and the tumor size and/or margin status.

Thus, women with four or more positive axillary nodes should receive radiation to the chest wall and infraclavicular region, supraclavicular area, internal mammary nodes, and any at-risk part of the axillary bed. If adjuvant chemotherapy is prescribed, radiation usually is given following chemotherapy completion.

For women with one to three positive axillary nodes, the guidelines urge clinicians to “strongly consider” treating them as they would women with four or more positive nodes. The same advice applies to women with negative nodes but tumors larger than 5 cm or positive surgical margins as defined by ink on tumor.

For patients with negative nodes, tumors 5 cm or smaller and negative but narrow margins (less than 1 mm), the guidelines recommend consideration of radiation to the chest wall. Patients with small tumors, no nodal involvement, and margins 1 mm or greater can be spared radiation therapy.

Recurrence

For women with local-only recurrence, the guidelines recommend mastectomy with axillary lymph node staging for those with recurrences after initial lumpectomy and radiation, or if the initial treatment was mastectomy with no radiation, surgical resection with radiation, or surgical resection alone for those women previously treated with mastectomy and radiation.

For regional or locoregional recurrences, the guidelines recommend that axillary recurrences be treated with surgery and radiation if possible, and that supraclavicular or internal mammary node recurrences be treated with radiation therapy, if possible.

HOLLYWOOD, FLA. – No huge surprises here, but newly revised National Comprehensive Cancer Network guidelines for locoregional therapy of breast cancer help clarify the optimal use of adjuvant radiation.

For example, updates to the pages on principles of radiation therapy in invasive breast cancer contain new information on optimal dosing, fractionation, treatment planning, and techniques for minimizing radiation of surrounding normal tissues, noted Dr. Kilian E. Salerno, director of breast radiation and soft tissue/melanoma radiation at the Roswell Park Cancer Institute in Buffalo, New York.

“There are a number of treatment options, many more now than ever before,” she said at the annual conference of the National Comprehensive Cancer Network.

The guidelines emphasize the importance of individualized radiation therapy planning and delivery. A CT-based treatment plan can help clinicians choose target volumes and identify adjacent organs and tissues that may be at risk for radiation spill.

Recommended options for reducing radiation doses to adjacent tissues include deep breath holds and prone positioning so that the treated breast hangs down, helping to isolate it from the heart and lungs.

Whole breast irradiation

Whole breast irradiation is the standard for radiation therapy of early breast cancer following breast-conserving surgery, although partial breast irradiation, typically of lumpectomy cavities, is also commonly performed, Dr. Salerno said.

Boost radiation in conjunction with breast conserving therapy can be delivered via en face electron fields, photons, or brachytherapy; boost dosing to chest wall scar is usually treated with photons or electrons, the guidelines note.

The guidelines recommend weekly imaging to ensure that daily treatment setup is consistent, but caution against routine use of daily imaging.

For whole breast irradiation, the guidelines recommend either doses of 46-50 Gy divided into 23-25 fractions (conventional fractionation), or, preferably, hypofractionated radiation delivered in doses of 40-42.5 Gy over 15-16 fractions, with all doses given 5 days per week. Patients at higher risk for recurrence should receive boost doses to the tumor bed, typically at doses of 10-16 Gy delivered in 4-8 fractions.

The guidelines now favor hypofractionation based on long-term results from clinical trials conducted in Ontario, Canada, and in London.

In the Canadian trial (N Engl J Med. 2010;362:513-20), patients were treated with whole-breast irradiation at doses of 42.5 Gy in 16 fractions, with no boost dose.

In the Standardisation of Breast Radiotherapy B (START B) trial (Lancet Oncol. 14;11:1086-94), in London, patients received 40 Gy in 15 fractions without a boost dose.

Both trials showed that hypofractionation was associated with disease outcomes that were equivalent or better to those seen with conventional fractionation schedules, as well as equivalent or better cosmesis and adverse event profiles, Dr. Salerno said.

“This is for whole breast radiation; it is not to be routinely used in the post-mastectomy setting or when you’re treating regional nodes,” she said.

Accelerated partial breast irradiation

For accelerated partial breast irradiation (APBI), the guidelines recommend a hypofractionated schedule of 34 Gy divided into 10 fractions delivered twice daily for 5 days for brachytherapy, or 38.5 Gy in 10 twice daily fractions with external beam therapy to the tumor bed.

The NCCN guidelines for APBI are based on the American Society of Radiation Oncology (ASTRO) consensus statement for APBI. An updated statement is planned for 2017.

Omit radiation?

Results from the CALGB 9343 trial and other studies suggest that in selected women with lower risk for recurrence, radiation can be omitted without compromising survival. These include women aged 70 or older with small primary breast cancers, negative nodes, negative surgical margins, and hormone-receptor-positive disease who are treated with breast conserving surgery and go on to tamoxifen maintenance.

Post-mastectomy radiation

Following total mastectomy with surgical axillary staging, with our without reconstruction, the guidelines recommend specific steps based on the number of nodes involved and the tumor size and/or margin status.

Thus, women with four or more positive axillary nodes should receive radiation to the chest wall and infraclavicular region, supraclavicular area, internal mammary nodes, and any at-risk part of the axillary bed. If adjuvant chemotherapy is prescribed, radiation usually is given following chemotherapy completion.

For women with one to three positive axillary nodes, the guidelines urge clinicians to “strongly consider” treating them as they would women with four or more positive nodes. The same advice applies to women with negative nodes but tumors larger than 5 cm or positive surgical margins as defined by ink on tumor.

For patients with negative nodes, tumors 5 cm or smaller and negative but narrow margins (less than 1 mm), the guidelines recommend consideration of radiation to the chest wall. Patients with small tumors, no nodal involvement, and margins 1 mm or greater can be spared radiation therapy.

Recurrence

For women with local-only recurrence, the guidelines recommend mastectomy with axillary lymph node staging for those with recurrences after initial lumpectomy and radiation, or if the initial treatment was mastectomy with no radiation, surgical resection with radiation, or surgical resection alone for those women previously treated with mastectomy and radiation.

For regional or locoregional recurrences, the guidelines recommend that axillary recurrences be treated with surgery and radiation if possible, and that supraclavicular or internal mammary node recurrences be treated with radiation therapy, if possible.

HOLLYWOOD, FLA. – No huge surprises here, but newly revised National Comprehensive Cancer Network guidelines for locoregional therapy of breast cancer help clarify the optimal use of adjuvant radiation.

For example, updates to the pages on principles of radiation therapy in invasive breast cancer contain new information on optimal dosing, fractionation, treatment planning, and techniques for minimizing radiation of surrounding normal tissues, noted Dr. Kilian E. Salerno, director of breast radiation and soft tissue/melanoma radiation at the Roswell Park Cancer Institute in Buffalo, New York.

“There are a number of treatment options, many more now than ever before,” she said at the annual conference of the National Comprehensive Cancer Network.

The guidelines emphasize the importance of individualized radiation therapy planning and delivery. A CT-based treatment plan can help clinicians choose target volumes and identify adjacent organs and tissues that may be at risk for radiation spill.

Recommended options for reducing radiation doses to adjacent tissues include deep breath holds and prone positioning so that the treated breast hangs down, helping to isolate it from the heart and lungs.

Whole breast irradiation

Whole breast irradiation is the standard for radiation therapy of early breast cancer following breast-conserving surgery, although partial breast irradiation, typically of lumpectomy cavities, is also commonly performed, Dr. Salerno said.

Boost radiation in conjunction with breast conserving therapy can be delivered via en face electron fields, photons, or brachytherapy; boost dosing to chest wall scar is usually treated with photons or electrons, the guidelines note.

The guidelines recommend weekly imaging to ensure that daily treatment setup is consistent, but caution against routine use of daily imaging.

For whole breast irradiation, the guidelines recommend either doses of 46-50 Gy divided into 23-25 fractions (conventional fractionation), or, preferably, hypofractionated radiation delivered in doses of 40-42.5 Gy over 15-16 fractions, with all doses given 5 days per week. Patients at higher risk for recurrence should receive boost doses to the tumor bed, typically at doses of 10-16 Gy delivered in 4-8 fractions.

The guidelines now favor hypofractionation based on long-term results from clinical trials conducted in Ontario, Canada, and in London.

In the Canadian trial (N Engl J Med. 2010;362:513-20), patients were treated with whole-breast irradiation at doses of 42.5 Gy in 16 fractions, with no boost dose.

In the Standardisation of Breast Radiotherapy B (START B) trial (Lancet Oncol. 14;11:1086-94), in London, patients received 40 Gy in 15 fractions without a boost dose.

Both trials showed that hypofractionation was associated with disease outcomes that were equivalent or better to those seen with conventional fractionation schedules, as well as equivalent or better cosmesis and adverse event profiles, Dr. Salerno said.

“This is for whole breast radiation; it is not to be routinely used in the post-mastectomy setting or when you’re treating regional nodes,” she said.

Accelerated partial breast irradiation

For accelerated partial breast irradiation (APBI), the guidelines recommend a hypofractionated schedule of 34 Gy divided into 10 fractions delivered twice daily for 5 days for brachytherapy, or 38.5 Gy in 10 twice daily fractions with external beam therapy to the tumor bed.

The NCCN guidelines for APBI are based on the American Society of Radiation Oncology (ASTRO) consensus statement for APBI. An updated statement is planned for 2017.

Omit radiation?

Results from the CALGB 9343 trial and other studies suggest that in selected women with lower risk for recurrence, radiation can be omitted without compromising survival. These include women aged 70 or older with small primary breast cancers, negative nodes, negative surgical margins, and hormone-receptor-positive disease who are treated with breast conserving surgery and go on to tamoxifen maintenance.

Post-mastectomy radiation

Following total mastectomy with surgical axillary staging, with our without reconstruction, the guidelines recommend specific steps based on the number of nodes involved and the tumor size and/or margin status.

Thus, women with four or more positive axillary nodes should receive radiation to the chest wall and infraclavicular region, supraclavicular area, internal mammary nodes, and any at-risk part of the axillary bed. If adjuvant chemotherapy is prescribed, radiation usually is given following chemotherapy completion.

For women with one to three positive axillary nodes, the guidelines urge clinicians to “strongly consider” treating them as they would women with four or more positive nodes. The same advice applies to women with negative nodes but tumors larger than 5 cm or positive surgical margins as defined by ink on tumor.

For patients with negative nodes, tumors 5 cm or smaller and negative but narrow margins (less than 1 mm), the guidelines recommend consideration of radiation to the chest wall. Patients with small tumors, no nodal involvement, and margins 1 mm or greater can be spared radiation therapy.

Recurrence

For women with local-only recurrence, the guidelines recommend mastectomy with axillary lymph node staging for those with recurrences after initial lumpectomy and radiation, or if the initial treatment was mastectomy with no radiation, surgical resection with radiation, or surgical resection alone for those women previously treated with mastectomy and radiation.

For regional or locoregional recurrences, the guidelines recommend that axillary recurrences be treated with surgery and radiation if possible, and that supraclavicular or internal mammary node recurrences be treated with radiation therapy, if possible.

HOLLYWOOD, FLA. – The latest updates to the National Comprehensive Cancer Network guidelines on breast cancer reflect a more nuanced approach to the use of systemic therapy in both the pre- and postoperative settings, with increasing emphasis on tailoring therapies to the unique clinical profiles of individual patients, according to Dr. William Gradishar.

The revised guidelines include new recommendations about preoperative endocrine and HER2-directed therapies, optimizing adjuvant endocrine therapy in both pre- and postmenopausal women, targeted agents as partner drugs for endocrine therapy in women with metastatic breast cancer, and recommendations about preservation of fertility in younger patients, said Dr. Gradishar, chair of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago.

“There have been some tweaks but I wouldn’t say major, major changes within the guidelines,” he said at the annual conference of the National Comprehensive Cancer Network.

Neoadjuvant therapy

One of the larger changes to this year’s guidelines is the addition of a page devoted to the principles of preoperative systemic therapy. The guidelines note that randomized clinical trials have shown similar long-term outcomes when patients receive the same treatment in either the pre- or post-op setting.

They add, however, that neoadjuvant systemic therapy “can render surgically inoperable tumors operable and offers potential benefits for patients with operable breast cancer. Importantly, preoperative systemic therapy can improve rates of breast conservation therapy eligibility and provides an opportunity to observe clinical and pathologic response to systemic therapy in an individual patient.”

The guidelines also note that a pathologic complete response to preoperative systemic therapy is predictive of “extremely favorable” disease-free and overall survival.

Patients who may be good candidates for neoadjuvant endocrine therapy include those with estrogen receptor–rich tumors (Allred score, 7 or 8), older postmenopausal women, and younger, premenopausal women with significant comorbidities that may make them poor candidates for chemotherapy, Dr. Gradishar said.

Adjuvant therapy

Regarding adjuvant therapy, the guidelines reflect data from recent clinical trials showing the benefits of both extended tamoxifen therapy, and for women who are premenopausal at diagnosis and are at high risk of recurrence, an aromatase inhibitor (AI) or steroidal aromatase inactivator plus ovarian suppression or ablation.

The recommendation to consider an AI and ovarian suppression in this population is based on data from the SOFT and TEXT trials (N Engl J Med. 2014; 371:107-18), which showed a significant reduction in the recurrence of hormone receptor–positive early breast cancer in premenopausal women treated with exemestane (Aromasin) and ovarian suppression, compared with tamoxifen and ovarian suppression.

Although data supporting the use of endocrine therapy and ovarian suppression are compelling, “we have to individualize our choice of which patient is appropriate for this, because there is a price to pay in terms of side effects, and we have to figure out if that balance is right for an individual patient,” Dr. Gradishar commented.

Anti-HER2 therapy

The guidelines state that patients with HER2-positive tumors should receive neoadjuvant systemic therapy with trastuzumab (Herceptin) for at least 9 weeks prior to surgery. For patients with stage T2 or greater or nodal status N1 or greater HER2-positive disease, a pertuzumab (Perjeta)-containing regimen may be considered.

Recurrent/Stage IV disease

Premenopausal women with recurrent or stage IV hormone receptor–positive disease should have ovarian ablation or suppression, and then be treated with a regimen for postmenopausal women, the guidelines say. Agents used in therapy for advanced disease have included a nonsteroidal or steroidal AI, a combination of exmestane and everolimus, palbociclib (Ibrance) plus letrozole (Femara), palbociclib plus fulvestrant, tamoxifen, or toremafine, megesterol acetate fluoxymesterone, or ethinyl estradiol.

The updated guidelines note that “a single study (S0226) in women with hormone receptor–positive breast cancer and no prior chemotherapy, biological therapy, or endocrine therapy for metastatic disease demonstrated that the addition of fulvestrant to anastrozole resulted in prolongation of time to progression. Subset analysis suggested that patients without prior adjuvant tamoxifen and more than 10 years since diagnosis experienced the greatest benefit. Two studies with similar design (FACT and SOFEA) demonstrated no advantage in time to progression with the addition of fulvestrant to anastrozole.”

Chemotherapy regimens for recurrent/metastatic breast cancer include various combination regimens, as well as single-agent therapy with anthracyclines, taxanes, antimetabolites, or microtubule inhibitors (all of the above preferred single agents), or with cyclophosphamide, carboplatin, docetaxel, albumin-bound paclitaxel, cisplatin, epirubicin, or ixabepilone.

For HER2-positive disease, preferred agents include pertuzumab and trastuzumab with either docetaxel (category 1 recommendation) or paclitaxel. Trastuzumab can also be combined with other agents such as paclitaxel with or without cisplatin, docetaxel, vinorelbine, or capecitabine.

For patients with recurrent HER2-positve disease with prior trastuzumab exposure, combinations may include lapatinin with capecitabine, or trastuzumab with capecitabine, lapatinib (without cytoxic therapy), or other agents.

Fertility preservation

Lastly, the revised guidelines note that all premenopausal patients should be informed about the potential effects of chemotherapy on fertility, with women who express the wish to have future pregnancies referred to fertility specialists. The options presented should be “based on patient specifics, disease stage, and biology (which determine the urgency and type and sequence of treatment). Timing and duration allowed for fertility preservation, options inclusive of oocyte and embryo cryopreservation as well as evolving technologies, and the probability of successful pregnancies subsequent to completion of breast cancer therapy are also to be discussed,” the guidelines say.

HOLLYWOOD, FLA. – The latest updates to the National Comprehensive Cancer Network guidelines on breast cancer reflect a more nuanced approach to the use of systemic therapy in both the pre- and postoperative settings, with increasing emphasis on tailoring therapies to the unique clinical profiles of individual patients, according to Dr. William Gradishar.

The revised guidelines include new recommendations about preoperative endocrine and HER2-directed therapies, optimizing adjuvant endocrine therapy in both pre- and postmenopausal women, targeted agents as partner drugs for endocrine therapy in women with metastatic breast cancer, and recommendations about preservation of fertility in younger patients, said Dr. Gradishar, chair of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago.

“There have been some tweaks but I wouldn’t say major, major changes within the guidelines,” he said at the annual conference of the National Comprehensive Cancer Network.

Neoadjuvant therapy

One of the larger changes to this year’s guidelines is the addition of a page devoted to the principles of preoperative systemic therapy. The guidelines note that randomized clinical trials have shown similar long-term outcomes when patients receive the same treatment in either the pre- or post-op setting.

They add, however, that neoadjuvant systemic therapy “can render surgically inoperable tumors operable and offers potential benefits for patients with operable breast cancer. Importantly, preoperative systemic therapy can improve rates of breast conservation therapy eligibility and provides an opportunity to observe clinical and pathologic response to systemic therapy in an individual patient.”

The guidelines also note that a pathologic complete response to preoperative systemic therapy is predictive of “extremely favorable” disease-free and overall survival.

Patients who may be good candidates for neoadjuvant endocrine therapy include those with estrogen receptor–rich tumors (Allred score, 7 or 8), older postmenopausal women, and younger, premenopausal women with significant comorbidities that may make them poor candidates for chemotherapy, Dr. Gradishar said.

Adjuvant therapy

Regarding adjuvant therapy, the guidelines reflect data from recent clinical trials showing the benefits of both extended tamoxifen therapy, and for women who are premenopausal at diagnosis and are at high risk of recurrence, an aromatase inhibitor (AI) or steroidal aromatase inactivator plus ovarian suppression or ablation.

The recommendation to consider an AI and ovarian suppression in this population is based on data from the SOFT and TEXT trials (N Engl J Med. 2014; 371:107-18), which showed a significant reduction in the recurrence of hormone receptor–positive early breast cancer in premenopausal women treated with exemestane (Aromasin) and ovarian suppression, compared with tamoxifen and ovarian suppression.

Although data supporting the use of endocrine therapy and ovarian suppression are compelling, “we have to individualize our choice of which patient is appropriate for this, because there is a price to pay in terms of side effects, and we have to figure out if that balance is right for an individual patient,” Dr. Gradishar commented.

Anti-HER2 therapy

The guidelines state that patients with HER2-positive tumors should receive neoadjuvant systemic therapy with trastuzumab (Herceptin) for at least 9 weeks prior to surgery. For patients with stage T2 or greater or nodal status N1 or greater HER2-positive disease, a pertuzumab (Perjeta)-containing regimen may be considered.

Recurrent/Stage IV disease

Premenopausal women with recurrent or stage IV hormone receptor–positive disease should have ovarian ablation or suppression, and then be treated with a regimen for postmenopausal women, the guidelines say. Agents used in therapy for advanced disease have included a nonsteroidal or steroidal AI, a combination of exmestane and everolimus, palbociclib (Ibrance) plus letrozole (Femara), palbociclib plus fulvestrant, tamoxifen, or toremafine, megesterol acetate fluoxymesterone, or ethinyl estradiol.

The updated guidelines note that “a single study (S0226) in women with hormone receptor–positive breast cancer and no prior chemotherapy, biological therapy, or endocrine therapy for metastatic disease demonstrated that the addition of fulvestrant to anastrozole resulted in prolongation of time to progression. Subset analysis suggested that patients without prior adjuvant tamoxifen and more than 10 years since diagnosis experienced the greatest benefit. Two studies with similar design (FACT and SOFEA) demonstrated no advantage in time to progression with the addition of fulvestrant to anastrozole.”

Chemotherapy regimens for recurrent/metastatic breast cancer include various combination regimens, as well as single-agent therapy with anthracyclines, taxanes, antimetabolites, or microtubule inhibitors (all of the above preferred single agents), or with cyclophosphamide, carboplatin, docetaxel, albumin-bound paclitaxel, cisplatin, epirubicin, or ixabepilone.

For HER2-positive disease, preferred agents include pertuzumab and trastuzumab with either docetaxel (category 1 recommendation) or paclitaxel. Trastuzumab can also be combined with other agents such as paclitaxel with or without cisplatin, docetaxel, vinorelbine, or capecitabine.

For patients with recurrent HER2-positve disease with prior trastuzumab exposure, combinations may include lapatinin with capecitabine, or trastuzumab with capecitabine, lapatinib (without cytoxic therapy), or other agents.

Fertility preservation

Lastly, the revised guidelines note that all premenopausal patients should be informed about the potential effects of chemotherapy on fertility, with women who express the wish to have future pregnancies referred to fertility specialists. The options presented should be “based on patient specifics, disease stage, and biology (which determine the urgency and type and sequence of treatment). Timing and duration allowed for fertility preservation, options inclusive of oocyte and embryo cryopreservation as well as evolving technologies, and the probability of successful pregnancies subsequent to completion of breast cancer therapy are also to be discussed,” the guidelines say.

HOLLYWOOD, FLA. – The latest updates to the National Comprehensive Cancer Network guidelines on breast cancer reflect a more nuanced approach to the use of systemic therapy in both the pre- and postoperative settings, with increasing emphasis on tailoring therapies to the unique clinical profiles of individual patients, according to Dr. William Gradishar.

The revised guidelines include new recommendations about preoperative endocrine and HER2-directed therapies, optimizing adjuvant endocrine therapy in both pre- and postmenopausal women, targeted agents as partner drugs for endocrine therapy in women with metastatic breast cancer, and recommendations about preservation of fertility in younger patients, said Dr. Gradishar, chair of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago.

“There have been some tweaks but I wouldn’t say major, major changes within the guidelines,” he said at the annual conference of the National Comprehensive Cancer Network.

Neoadjuvant therapy

One of the larger changes to this year’s guidelines is the addition of a page devoted to the principles of preoperative systemic therapy. The guidelines note that randomized clinical trials have shown similar long-term outcomes when patients receive the same treatment in either the pre- or post-op setting.

They add, however, that neoadjuvant systemic therapy “can render surgically inoperable tumors operable and offers potential benefits for patients with operable breast cancer. Importantly, preoperative systemic therapy can improve rates of breast conservation therapy eligibility and provides an opportunity to observe clinical and pathologic response to systemic therapy in an individual patient.”

The guidelines also note that a pathologic complete response to preoperative systemic therapy is predictive of “extremely favorable” disease-free and overall survival.

Patients who may be good candidates for neoadjuvant endocrine therapy include those with estrogen receptor–rich tumors (Allred score, 7 or 8), older postmenopausal women, and younger, premenopausal women with significant comorbidities that may make them poor candidates for chemotherapy, Dr. Gradishar said.

Adjuvant therapy

Regarding adjuvant therapy, the guidelines reflect data from recent clinical trials showing the benefits of both extended tamoxifen therapy, and for women who are premenopausal at diagnosis and are at high risk of recurrence, an aromatase inhibitor (AI) or steroidal aromatase inactivator plus ovarian suppression or ablation.

The recommendation to consider an AI and ovarian suppression in this population is based on data from the SOFT and TEXT trials (N Engl J Med. 2014; 371:107-18), which showed a significant reduction in the recurrence of hormone receptor–positive early breast cancer in premenopausal women treated with exemestane (Aromasin) and ovarian suppression, compared with tamoxifen and ovarian suppression.

Although data supporting the use of endocrine therapy and ovarian suppression are compelling, “we have to individualize our choice of which patient is appropriate for this, because there is a price to pay in terms of side effects, and we have to figure out if that balance is right for an individual patient,” Dr. Gradishar commented.

Anti-HER2 therapy

The guidelines state that patients with HER2-positive tumors should receive neoadjuvant systemic therapy with trastuzumab (Herceptin) for at least 9 weeks prior to surgery. For patients with stage T2 or greater or nodal status N1 or greater HER2-positive disease, a pertuzumab (Perjeta)-containing regimen may be considered.

Recurrent/Stage IV disease

Premenopausal women with recurrent or stage IV hormone receptor–positive disease should have ovarian ablation or suppression, and then be treated with a regimen for postmenopausal women, the guidelines say. Agents used in therapy for advanced disease have included a nonsteroidal or steroidal AI, a combination of exmestane and everolimus, palbociclib (Ibrance) plus letrozole (Femara), palbociclib plus fulvestrant, tamoxifen, or toremafine, megesterol acetate fluoxymesterone, or ethinyl estradiol.

The updated guidelines note that “a single study (S0226) in women with hormone receptor–positive breast cancer and no prior chemotherapy, biological therapy, or endocrine therapy for metastatic disease demonstrated that the addition of fulvestrant to anastrozole resulted in prolongation of time to progression. Subset analysis suggested that patients without prior adjuvant tamoxifen and more than 10 years since diagnosis experienced the greatest benefit. Two studies with similar design (FACT and SOFEA) demonstrated no advantage in time to progression with the addition of fulvestrant to anastrozole.”

Chemotherapy regimens for recurrent/metastatic breast cancer include various combination regimens, as well as single-agent therapy with anthracyclines, taxanes, antimetabolites, or microtubule inhibitors (all of the above preferred single agents), or with cyclophosphamide, carboplatin, docetaxel, albumin-bound paclitaxel, cisplatin, epirubicin, or ixabepilone.

For HER2-positive disease, preferred agents include pertuzumab and trastuzumab with either docetaxel (category 1 recommendation) or paclitaxel. Trastuzumab can also be combined with other agents such as paclitaxel with or without cisplatin, docetaxel, vinorelbine, or capecitabine.

For patients with recurrent HER2-positve disease with prior trastuzumab exposure, combinations may include lapatinin with capecitabine, or trastuzumab with capecitabine, lapatinib (without cytoxic therapy), or other agents.

Fertility preservation

Lastly, the revised guidelines note that all premenopausal patients should be informed about the potential effects of chemotherapy on fertility, with women who express the wish to have future pregnancies referred to fertility specialists. The options presented should be “based on patient specifics, disease stage, and biology (which determine the urgency and type and sequence of treatment). Timing and duration allowed for fertility preservation, options inclusive of oocyte and embryo cryopreservation as well as evolving technologies, and the probability of successful pregnancies subsequent to completion of breast cancer therapy are also to be discussed,” the guidelines say.