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Purpose of Review Young women who carry a genetic predisposition to breast cancer need to balance surgical and nonsurgical risk reducing options with childbearing. In this review, we explore how women make decisions without the benefit of official guidelines and in the context of frequently contradictory strategies. Recent Findings Women of reproductive age with known BRCA mutations receive incomplete and conflicting advice regarding the urgency and timing of risk reducing mastectomy (RRM). Those who prioritize RRM achieve highly effective prevention and thereby avoid not only a diagnosis of breast cancer but also adjuvant therapies which limit future childbearing. All reconstructive options are available and high levels of satisfaction are reported. Those who delay prophylactic mastectomy can pursue nonsurgical breast and ovarian risk reduction strategies such as tamoxifen and oral contraception, yet these delay child bearing. Women who prioritize child bearing maintain the ability to breast feed but have limited screening options during pregnancy and lactation. Summary Prioritization and timing of risk reduction and childbearing in young BRCA positive women is challenging. Elucidating these challenges enables clinicians to better counsel these women.

This review aims to present contemporary research regarding the association between genetic/germline African ancestry and risk of triple negative breast cancer (TNBC). TNBC is more common in African American compared to White American women and contributes to breast cancer outcome disparities. Variation in the frequency of TNBC across different regions of Africa suggests that population migration (the African diaspora) and the genetics of African ancestry contribute to this epidemiology. Our group has coined the nomenclature “oncologic anthropology” to describe the study of these global breast cancer patterns. Cancer-associated founder mutations which have been identified for most ancestral heritage groups represent examples of oncologic anthropology. Herein, we present the expanding body of research related to the Duffy antigen receptor for chemokines (DARC)/atypical chemokine receptor 1 (ACKR1) and its association with cancer-related cytokines as a factor in the etiology of differences in breast cancer burden. DARC/ACKR1 expression on erythrocytes is also widely known as the “Duffy blood group,” and the genotype resulting in its absence (Duffy-null) was under strong evolutionary selection pressure in western, sub-Saharan Africa several thousand years ago because of the protection afforded by this phenotype against malaria pathogens. The Duffy-null allele is therefore nearly fixed among populations in this region of Africa, and it has varying prevalence among populations with admixed western sub-Saharan African ancestry (such as African Americans and East Africans). Recently characterized associations between an African ancestry-specific DARC/ACKR1 variant, breast tumor DARC/ACKR1 expression, and DARC/ACKR1 influence on cancer-associated chemokines indicate that this gene is important in understanding disease progression as well as breast cancer disparities.

Data generated from well-designed clinical trials represent a powerful strategy for advancing cancer care. African Americans carry a disproportionately high breast cancer mortality burden and have been under-represented in clinical trial research. This review summarizes accrual patterns for clinical trials studying prevention, medical oncology, surgical oncology and radiation oncology in breast cancer. Strengthening the diversity of breast cancer clinical trial participants can improve understanding of the multifactorial etiology of breast cancer disparities. Strategies to achieve this goal include optimizing utilization of patient navigation services, addressing the financial toxicity of clinical trial participation and educating both patients and providers regarding the importance of accrual diversity. Clinical trialists should work in partnership with disparity researchers and advocates to ensure that protocols are designed to address disparity questions, to reach diverse population subsets and to overcome financial barriers to participation.

Purpose of Review This review summarizes the most recent data on the management of small, node-negative Her2+ and triple-negative breast cancer. Recent Findings Both Her2+ and triple-negative breast cancers are characterized by high rates of recurrence and worse survival outcomes compared to hormone-positive cancers. De-escalation of systemic therapy in early-stage breast cancer is a recent national trend in clinical research. Recent prospective trials support the scaling back of cytotoxic agents and maximization of targeted therapy regimens. Similarly, large retrospective studies on small, node-negative triple-negative breast cancer report the omission of chemotherapy in women with T1a,N0 triple-negative cancers with favorable short term outcomes. Summary De-escalation of systemic therapy for Her2+ breast cancer is effective in the management of early-stage, node-negative disease. Future prospective studies on the omission of systemic therapy for triple-negative breast cancer are required to safely adopt into consensus guidelines.

Triple negative breast cancer (TNBC) is an aggressive subtype with frequent chemotherapy resistance. In recent years, advances in immunotherapy have yielded promising new therapeutic strategies for the treatment of TNBC; studies evaluating immune check point inhibitors (ICIs) in combination with chemotherapy have shown encouraging results in both early and advanced stages of disease. Atezolizumab plus nab-paclitaxel resulted in improved progression-free survival (PFS) and overall survival (OS) compared to nab-paclitaxel alone in patients with programmed death-ligand 1-positive (PD-L1+) metastatic TNBC (mTNBC). However, atezolizumab plus paclitaxel did not improve outcomes. Pembrolizumab plus chemotherapy improved PFS compared to chemotherapy alone in patients with PD-L1+ mTNBC, and follow-up for OS is ongoing. The addition of pembrolizumab and atezolizumab to neoadjuvant chemotherapy increased pathologic complete response rates, regardless of PD-L1 status, and event-free survival is pending. Several other combinations of ICIs with targeted agents are under investigation to enhance the host immune response and are discussed in this review. TNBC has a poor prognosis with limited treatment options. Recent studies have demonstrated encouraging results by adding ICIs to chemotherapy, although optimal combinations remain to be defined. In this review, we highlight advances in TNBC treatment including ICIs and targeted agents and also discuss future directions.

PURPOSE OF REVIEW: In this review, we discuss targets of interest in Triple-negative breast cancer (TNBC), approved targeted agents and the results of the clinical trials that led to their approval. Additionally, we review ongoing clinical trials evaluating the use of novel targeted agents in the treatment of TNBC. RECENT FINDINGS: TNBC accounts for 15–20% of all breast cancer cases and is associated with worse clinical outcomes. Patients have a higher risk of metastatic recurrence and inferior overall survival compared to other breast cancer subtypes. Cytotoxic chemotherapy has historically been the mainstay of treatment for TNBC. In recent years, we have seen a surge in clinical trials investigating the use of targeted agents in TNBC and now have approval for targeted therapies in select patients. Inhibitors of PARP (olaparib and talazoparib), PD-L1 (atezolizumab) and an antibody drug conjugate targeting Trop-2 (sacituzumab govitecan-hziy) are now approved for the use in select groups of patients with TNBC. SUMMARY: Various novel targeted agents as monotherapy, dual targeted combinations, and chemotherapy combinations are currently under investigation. The results are promising and may significantly improve patient outcomes in TNBC.

Purpose of review The COVID-19 pandemic has had a devastating impact on virtually all aspects of the healthcare system, including oncology clinical trials. The purpose of this review is to describe the impact of the pandemic on national breast cancer clinical trials. Recent findings Of the 61 breast cancer–specific cooperative group breast cancer clinical trials open to accrual during the pandemic, 32% of them received supplementary tailored guidance regarding current and foreseeable challenges for clinical sites and investigators due to COVID-19. Many clinical trial sites reported decreases in enrollment and accrual, drastic disruptions to protocol, and challenges related to research infrastructure, staff burden, and assuring social distancing. Summary The challenges early in pandemic led to many operational changes in clinical trials, including use of electronic consent for enrollment, telemedicine visits, and mail order pharmacy. The pandemic highlighted aspects of breast cancer clinical trial that could be modernized while maintaining research integrity.

Adjuvant radiation represents a standard approach following breast conserving surgery. While traditionally delivered as whole breast irradiation (WBI), an alternative has emerged with the development of partial breast irradiation techniques. One such technique is intraoperative radiation therapy (IORT). The purpose of this review is to discuss the studies evaluating IORT as well as evaluating current guidelines and future directions. Review of two randomized trials (TARGIT-A and ELIOT) demonstrates that breast cancer patients treated with IORT had a higher risk of local recurrence (LR). However, patients with low-risk features and IORT performed at the time of surgery had similar rates of LR at 5 years, with longer follow-up needed. IORT as a boost is promising, and studies are ongoing. Further studies are needed to validate the role of IORT and which patients are appropriate for IORT, and longer follow-up is needed.

Purpose of Review Invasive lobular carcinoma (ILC) is increasingly recognized as a distinct subtype of breast cancer with unique management challenges. We reviewed currently available clinical trials for patients with ILC. Recent Findings We describe the rationale for and study design of clinical trials for patients with both early stage and metastatic ILC. Molecular alterations specific to or enriched in ILC may serve as treatment targets. Summary ILC has specific features that may be treatment targets. Clinical trials for ILC are available and being developed.

Purpose of Review Lobular carcinoma in situ (LCIS) encompasses classical LCIS and other rarer and more recently recognised variants, namely pleomorphic LCIS (PLCIS) and florid LCIS. Each of those entities has characteristic histological diagnostic criteria, different rates of underestimation of malignancy and recommended management. In addition, those lesions can mimic a number of benign and malignant breast lesions and can particularly be mistaken for ductal carcinoma in situ (DCIS). Accurate diagnosis of those lesions is critical to ensuring the appropriate patient management. Recent Findings Several international guidelines refining the pathological classification, staging and management of those lesions have recently been updated. This review will provide an up-to-date pathological overview of the current knowledge of LCIS with emphasis on the multidisciplinary management implications. Summary Close correlation between imaging and pathology in a multidisciplinary pathway is essential in LCIS management. Classical LCIS on core biopsy/vacuum-assisted biopsy (VAB) is coded as B3 and, if without discordant imaging, should further be sampled by vacuum-assisted excision (VAE). PLCIS should be coded and managed as per high-grade DCIS. Florid LCIS is a rare entity that is thought to be more aggressive than classical LCIS. Excision with clear margin is advised.

The role of locoregional treatment (LRT) in the setting of metastatic breast cancer (MBC) is widely debated due to conflicting results on the impact on outcomes. This review provides a brief overview and evaluation of current evidence. The majority of retrospective studies suggest LRT provides some survival benefit, but it is not known exactly which subgroup of patients would benefit the most. The significant concerns about inherent biases associated with these studies make interpretation of results challenging. Recent data from prospective clinical trials are conflicting and suggest that adding LRT to treatment regimens makes no difference to health-related quality of life. Based on the limited high-quality evidence, there is uncertainty that LRT improves outcomes in patients with MBC, and it should not become standard clinical practice. Further prospective research focused on whether subsets of patients benefit from LRT is required.

Pregnancy-associated breast cancer (PABC) is the most common malignancy diagnosed in women of childbearing age and is increasing in frequency as the average age of pregnancy rises. Outcomes for PABC are similar to age- and stage-matched controls. In this review, we discuss current treatment recommendations for PABC. Treatment of PABC involves complex coordination by a multi-disciplinary team of providers including surgical, radiation, and medical specialists. The timing and administration of these therapies must be tailored to account for the pregnancy in order to keep both woman and fetus safe. Additional data is needed on the safety of newer breast cancer therapies during pregnancy. With close oversight, breast cancer therapy can be delivered effectively for the patient and safely for the developing fetus.

Breast cancer is the most common malignancy diagnosed in women worldwide. As the average age of child-bearing increases, more women will not have started or completed their families at the time of a breast cancer diagnosis. The scope of this review is to present current practices for fertility preservation, evidence for such practices, and future directions for fertility counseling and treatment for women with breast cancer. In the face of multimodality treatment for breast cancer including surgery, gonadotoxic chemotherapies, and radiation, women who desire to become biological mothers face complex decisions, including the pursuit of fertility preservation prior to treatment which may be dictated by age, ovarian reserve, and the choice of systemic therapy. Several considerations impact the decision to pursue fertility preservation, and practices are continually advancing. This discussion is aimed at improving access and information on fertility preservation methods in breast cancer patients.

In patients undergoing mastectomy, benefits of nipple preservation include improved esthetics and quality of life. The purpose of this review is to evaluate the oncologic safety of nipple-sparing mastectomy (NSM) in women with breast cancer, focusing on complications, recurrence, and patient reported outcomes. Clinical presentation, risk factors for nipple involvement, and preoperative imaging may be helpful in choosing appropriate candidates. Recent series suggest that complications after NSM are slightly increased when compared to traditional mastectomy but likely related to increased risk of nipple necrosis. Pathologic assessment of the nipple is necessary. Local recurrence after NSM appears similar to patients after traditional mastectomy; however, studies evaluating local recurrence are of lower quality and have short follow-up. NSM is associated with improved psychosocial and sexual well-being after surgery. Studies evaluating oncologic safety of therapeutic NSM suggest that it is a viable option for appropriate patients, as risk of local recurrence and survival appears to be similar to patients undergoing traditional mastectomy. However, careful patient selection is critical.

Axillary primary breast cancer, also known as occult primary breast cancer, is a rare entity representing less than 1% of all breast cancers. The surgical management of the axilla in breast cancer has changed significantly, with implications for the management of axillary primary breast cancer. Much of the data is limited by era, small cohorts, or large retrospective database studies. The purpose of this review is to reinforce the diagnostic work up of occult breast cancer, review updated management strategies of the axilla and breast, and summarize changes and updates in practice management and outcomes. Pathologic confirmation of breast primary disease and MRI are critical for the diagnostic work up of axillary primary breast cancer. A recent axillary primary specific meta-analyses and several National Cancer Database studies (NCDB) have reinforced that mastectomy versus breast conservation with whole breast radiation has equivalent outcomes. Surgical axillary management is under evolution, with multiple large trials reporting the role of neoadjuvant chemotherapy to downstage the node-positive axilla and decrease the morbidity of axillary lymph node dissection by allowing accurate sentinel node biopsy. Use of neoadjuvant chemotherapy and adjuvant radiation therapy is increasingly used, although no prospective data exists specifically in occult primary breast cancer. Appropriate diagnostic work up includes MRI to identify possible primary breast lesions in all patients with metastatic axillary disease and negative exam, mammography, and ultrasound. Axillary primary breast cancer should be treated with contemporary management strategies as other anatomic stage II breast cancers. Appropriate management strategies based on recent trial data suggest the use of neoadjuvant chemotherapy to downstage the axilla and allow for less morbid axillary surgery. Outcomes are equivalent with mastectomy or whole breast radiation.

Radiation therapy remains an integral component in the treatment of all stages of breast cancer which is the leading cause of cancer worldwide for women. We aimed to identify and characterize clinical trials in radiation therapy that have led to changes in practice essential for every physician who treats breast cancer. Hypofractionation, accelerated partial breast irradiation, and prone positioning have led to shorter treatment times and decreased toxicity for early-stage breast cancer patients. For patients with nodal metastasis, regional nodal radiation has improved disease-free survival and local recurrence in most breast cancer subtypes. The role of radiation in metastatic disease is transitioning from palliation alone to ablative therapy in patients with oligometastatic disease. Radiation therapy remains a pillar in the management of breast cancer. Research published since 2015 has established new standards of care in the delivery of radiation therapy to breast cancer patients. Ongoing trials and future work seek to evaluate who benefits most, whom therapy can be avoided, and the expanding role in definitive treatment of metastatic disease.

Traditional breast-conserving surgery combined with whole breast radiation results in equivalent overall survival as total mastectomy, with the benefit of being less invasive with fewer surgical complications and faster recovery. However, the surgical defect in the breast parenchyma, when combined with whole breast radiation, can result in cosmetic deformities that many patients find distressing. Partial mastectomy performed using plastic/reconstructive surgical techniques with the goal of optimizing both oncologic and esthetic outcomes is referred to as oncoplastic (breast) surgery. Herein, the surgical complications, oncologic, esthetic, and quality of life outcomes of oncoplastic surgery are reviewed. Overall, the oncologic and surgical outcomes of oncoplastic surgery are similar to traditional partial mastectomy. The esthetic outcomes of oncoplastic surgery are, by design, objectively superior to that which can be achieved with standard partial mastectomy and translate into improved psychosocial quality of life for many women. Oncoplastic surgery provides patients with the benefit of improved cosmesis over traditional lumpectomy without compromising cancer treatment outcomes.

Breast density, or the amount of fibroglandular tissue in the breast, has become a recognized and independent marker for breast cancer risk. Public awareness of breast density as a possible risk factor for breast cancer has resulted in legislation for risk stratification purposes in many US states. This review will provide a comprehensive overview of the currently available imaging modalities for qualitative and quantitative breast density assessment and the current evidence on breast density and breast cancer risk assessment. To date, breast density assessment is mainly performed with mammography and to some extent with magnetic resonance imaging. Data indicate that computerized, quantitative techniques in comparison with subjective visual estimations are characterized by higher reproducibility and robustness. Breast density reduces the sensitivity of mammography due to a masking effect and is also a recognized independent risk factor for breast cancer. Standardized breast density assessment using automated volumetric quantitative methods has the potential to be used for risk prediction and stratification and in determining the best screening plan for each woman.

Purpose of the Study More than 50% of breast cancer survivors without a diagnosis of lymphedema suffer daily from numerous and co-occurring lymphedema symptoms. This study aimed to identify lymphedema symptom patterns and the association of such patterns with phenotypic characteristics and biomarkers using latent class analysis (LCA). A prospective, descriptive, and repeated-measure design was used to enroll 140 women and collect data. Recent Findings LCA identified three distinct lymphedema symptom classes at 8 weeks and 12 months post-surgery: low, moderate, and severe symptom classes and associated phenotypic characteristics. Participants were more likely to be in the severe symptom classes at 12 months post-surgery if they had lower education level, cording, an axillary syndrome at 8 weeks post-surgery, neoadjuvant chemotherapy, and radiation. Summary Pre-surgery level of IL1-a, IL-6, IL-8, and VEGF was associated with the severe symptom class at 8 weeks post-surgery, suggesting that such biomarkers may be used to predict risk for lymphedema symptoms.

Purpose of ReviewInflammatory breast cancer (IBC) is a biologically aggressive subtype with a high risk for rapid local progression and early distant metastasis. We review the updated data for optimal locoregional management of IBC, including areas of active controversy.Recent FindingsAdvancements in tri-modality therapies have improved survival among IBC patients in recent years; however, the risk of locoregional and distant recurrence remains high, particularly in triple-negative IBC. Data to support de-escalation of surgery or radiotherapy is limited, and the recommended treatment approach for non-metastatic IBC remains preoperative systemic therapy (PST), modified radical mastectomy (MRM), and adjuvant radiotherapy in all patients. For patients with de novo metastatic disease, locoregional intervention may be appropriate.SummaryOptimal locoregional management of IBC remains PST followed by MRM and adjuvant radiotherapy. With increasingly effective systemic therapies, research to identify a subset of patients who may benefit from de-escalation of locoregional therapies is warranted.

Many young women diagnosed with breast cancer will be confronted with premature ovarian insufficiency and infertility as a consequence of systemic therapies used to treat their cancer. This is a concern for nearly half of young women diagnosed with breast cancer. We will review the impact of breast cancer chemotherapy, endocrine therapy, and immunotherapy on fertility and surrogate markers of fertility. Modern breast cancer treatments continue to have an impact on a woman’s fertility potential. This risk is reduced as more patients are able to safely eliminate chemotherapy as part of their treatment plan without compromising cancer-related outcomes. Research is being done to assess whether patient outcomes are affected from pausing endocrine therapy to allow for pregnancy. With varying extent, most breast cancer treatments have some impact on fertility although more data is necessary. Individualized fertility counseling is an important aspect of comprehensive cancer care. This review highlights the special population of premenopausal breast cancer patients and the challenge in their care should they desire children.

Over the past decade, prospective clinical trials and retrospective data have changed clinical guidelines for the treatment of older patients, most notably those patients with early, hormone receptor-positive, clinically node-negative breast cancer. Here is a comprehensive review of the literature supporting de-escalation of local-regional therapy in older patients with breast cancer. The de-escalation of treatment in elderly patients includes minimizing surgical interventions and adjuvant radiation therapy. Current Choosing Wisely® guidelines recommend considering the omission of surgical staging of the axilla in patients ≥ 70 with early-stage, hormone receptor-positive breast cancer. Primary endocrine therapy may be a suitable option for older patients with hormone receptor-positive breast cancer and short life-expectancy. The long-term results of the CALGB 9343 clinical trial reveal that radiotherapy omission is not associated with a survival benefit in patients ≥ 70 with early-stage, hormone receptor-positive, node-negative breast cancer, who receive 5 years of adjuvant endocrine therapy. The results of the RAPID trial support that shorter courses of radiation therapy are non-inferior to standard therapy and may be of significant value to older patients who require radiation. In addition, intraoperative radiotherapy may be useful in older patients with mobility issues who have higher-risk tumors and the current TARGIT-E aims to assess IORT in patients ≥ 70 with hormone receptor-positive tumors. Select older patients with breast cancer may benefit from the omission of axillary staging, less aggressive breast surgery, and shorter courses or total omission of radiation therapy. Current studies aim to continue to define the appropriate criteria for which older patients can benefit from de-escalation of local-regional therapy.

Regional nodal recurrence (RNR) after breast cancer treatment is historically rare but associated with worse survival outcomes. The management of primary breast cancer has changed significantly, with less completion axillary dissection (ALND) and increased use of genomic testing, neoadjuvant therapy, and regional nodal irradiation. This review examines the incidence, risk factors, presentation, treatment, and prognosis of RNR in the context of modern breast cancer treatment. The rate of RNR recurrence is low (

Upfront fertility counseling improves quality of life for young breast cancer patients planning for pregnancy post-treatment. We reviewed the literature on the impact, if any, that breast radiation may have on post-treatment fertility and fertility preservation decisions in order to facilitate fertility counseling. While the ovaries and uterus should not receive significant doses of radiation during breast radiation, negligible radiation doses (that are too low to induce ovarian failure) may result from internal scatter. Despite a low risk of infertility from breast radiation, data suggest that women may have chosen mastectomy to avoid whole-breast radiation due to fertility concerns. Although multiple studies have provided encouraging data with successful pregnancies after breast cancer treatment, the number of patients that underwent breast radiation and required fertility preservation methods are rarely reported. In conclusion, the impact that breast radiation appears to have on fertility is low and, in our opinion, should not result in patients choosing mastectomy over breast conservation therapy due to fears of infertility. However, further studies specifying the patients receiving breast radiation and requiring fertility preservation methods are warranted to help reassure patients and their providers.

The purpose of this review is to describe and compare the use of oocyte donation, gestational carriers, and adoption for family building specifically in women with a history of breast cancer. Oocyte donation is an effective and safe option for women whose exposure to gonadotoxic cancer therapy has resulted in primary ovarian insufficiency, or for women with a familial cancer syndrome who are concerned about genetic risk to their offspring. A gestational carrier may also be considered—with or without oocyte donation—depending on the patient’s acceptance of ovarian stimulation and pregnancy in the context of prior breast cancer or ongoing endocrine therapy. Lastly, adoption is a frequently considered option for family building by many breast cancer survivors. Assisted reproductive technology and adoption offer breast cancer survivors the opportunity to expand their families despite the challenges that the diagnosis may pose.

In recent years, there have been a number of small, yet notable practice changes in the delivery of postmastectomy radiation therapy (PMRT) in breast cancer patients. Herein, we describe the role of PMRT and its evolving delivery with hypofractionated regimens. The UK START trials and whole-breast hypofractionation studies established the safety and effectiveness of accelerated radiotherapy. This has inspired further investigations of similar principles in patients with reconstruction, acute and late toxicities associated with hypofractionated regimens, socioeconomic benefit, and evolving delivery techniques. Overall, results from clinical trials evaluating hypofractionation for RNI or PMRT appear promising despite the limited length of follow-up. Ongoing clinical trials will provide valuable data on the safety of hypofractionation in breast cancer patients with immediate reconstruction. Hypofractionation for PMRT represents high-quality care that is not only more convenient for patients but also more cost-effective for the healthcare system.

Axillary nodal disease is significantly less likely in both clinically node-negative (cN0) and node-positive (cN+) breast cancer patients after neoadjuvant chemotherapy (NAC). There have thus been significant efforts to “de-escalate” axillary surgery in this setting. This review discusses modern axillary surgical paradigms and techniques after NAC. In cN0 patients, the accuracy and feasibility of sentinel lymph node biopsy (SLNB) after NAC is well-established, with prospective evidence supporting its oncologic safety. SLNB is also acceptable in select cN+ patients when certain criteria are met. There is mounting “real-world” evidence for the technical feasibility of this approach, including various methods of localizing and excising biopsy-proven nodes, with the ability to avoid axillary lymph node dissection in a substantial proportion of patients. However, outcome data is limited to small retrospective series. In appropriately selected patients, there is increasing opportunity to leverage the benefits of NAC to minimize the burden of axillary surgery.

To review postlumpectomy whole breast irradiation (WBI) in early-stage breast cancer with regard to the use of hypofractionation and a tumor bed boost. Hypofractionation is currently standard practice for most cases of postlumpectomy WBI. A boost is recommended for women at increased risk for local recurrence due to clinical or pathologic risk factors. A sequential boost is currently standard practice for WBI with either conventional or hypofractionated radiation. Phase I–II trials of hypofractionation and concurrent boost have shown comparably low risks for local recurrence and acute and late toxicity without adding additional treatment days to WBI. Postlumpectomy WBI with hypofractionation and concurrent boost is a promising method of gaining the local control benefit of a tumor bed boost but maintaining the shorter treatment length, lower cost, and convenience of hypofractionation. Phase III trials are pending that may make this approach more widely accepted practice.

To review the role of radiation therapy and specifically metastasis-directed stereotactic body radiation therapy (SBRT) in the management of patients with oligometastatic breast cancer with emphasis on potential toxicities and future directions. Recent prospective studies have demonstrated encouraging initial results indicating the potential efficacy of metastasis-directed SBRT in the management of patients with oligometastatic disease. However, given potentially significant toxicities associated with metastasis-directed SBRT, additional data in the form of phase III randomized control trials are needed to define the role of SBRT in the management of patients with oligometastatic breast cancer; such studies are currently ongoing. While current data are encouraging, additional data are required to determine the benefit of SBRT in patients with oligometastatic breast cancer. Physicians opting to treat patients with metastasis-directed SBRT should ideally do so on protocol.

What is the current evidence for the role of drugs as risk factors for the development of breast cancer–related lymphoedema (BCRL) and in exacerbating existing BCRL? What are the mechanisms by which these effects occur? There is now evidence that taking calcium channel blockers (CCBs) during and after breast cancer treatment and receiving docetaxel chemotherapy are risk factors for the development of BCRL. CCBs cause oedema by increasing capillary filtration and docetaxel by inhibiting lymphatic vessel contractions. Ideally, CCBs should be avoided during and after treatment for breast cancer, but alternative options include changing to CCBs with a lower risk of causing oedema. An awareness of the potential role of medications in increasing the risk of BCRL and exacerbating existing BCRL is important in the appropriate management of patients treated for breast cancer.

The use of neoadjuvant chemotherapy (NAC) for breast cancer (BC) can eradicate axillary disease in > 40% of patients. The standard of care for node-positive BC has been axillary lymph node dissection. In this review, we examine the data for de-escalating axillary surgery after NAC. Studies have shown that sentinel lymph node biopsy (SLNB) is accurate after NAC. False negative rates (FNR) of SLNB after NAC in node-positive patients have been reduced with a combination of dual tracers and localization of the clipped positive node. Clipped nodes may be localized with a variety of methods. Targeted axillary dissection (removal of clipped node in conjunction with SLNB) results in an acceptable FNR and can be considered in certain patients with axillary clinical response to neoadjuvant chemotherapy. Patient selection is important, as those with persistently positive nodes on clinical exam should proceed directly to axillary dissection.

Upper extremity lymphedema is a much-feared complication of breast cancer treatment leading to significant impairments in patients’ quality of life. The mainstay of treatment for this debilitating chronic disease has been non-surgical modalities, namely complete decongestive therapies. Surgical treatment of lymphedema has emerged as an option for patients who have exhausted these conservative measures and consists of both physiologic procedures (vascularized lymph node transplant and lymphovenous bypass) which aim to reduce the burden of lymphatic fluid and reductive procedures to remove excess soft tissue. Opinions vary among surgeons regarding the appropriate surgical indications in patients with different stages of lymphedema for each type of surgery, as well as the optimal donor site for lymph node transplant, and recent studies are beginning to address these questions. Additionally, there is growing data regarding the benefits of preventative lymphatic surgery at the time of axillary lymph node dissection, as well as the cost effectiveness of this approach. Surgical approaches for the prevention and treatment of breast cancer–related lymphedema are gaining popularity as a means of improving patients’ quality of life. There is an expanding body of literature demonstrating the effectiveness of these surgical procedures in terms of reduction in arm circumference, decreased cellulitis incidence, and overall quality of life, as well as emerging evidence of their cost effectiveness.

Panel testing is increasingly being offered to patients. Currently, women may be offered a panel of up to 80 genes. Oncologists are tasked with understanding the indications for this testing as well as the potential implications. In this review, we outline which patients should undergo genetic testing for hereditary breast cancer, when this testing should be performed, and which genes should be tested for. Our understanding of hereditary breast cancer has drastically changed with the advent of next generation sequencing (NGS), and many additional genes have been associated with increased breast cancer risk. Some have advocated for genetic testing of all women with breast cancer. Routine genetic testing for all women with breast cancer is not warranted. Women with a phenotype associated with hereditary breast cancer, with a family history of cancer, or for whom a positive genetic test would change management should be offered genetic testing.

PURPOSE OF REVIEW: Despite a steady improvement in breast cancer survival rates over the past several decades, mortality disparities remain among Black women, who have a 42% higher death rate compared to non-Hispanic white (NHW) women. Hereditary breast cancer (HBC) accounts for 5–10% of all breast cancer cases, the majority of which are due to the BRCA1 and BRCA2 (BRCA) genes. Despite the availability of BRCA testing for over 25 years, there remain disproportionately lower rates of genetic testing among Blacks compared to NHW due to a multitude of factors. The intent of this review is to discuss racial disparities focused on HBC across diverse populations and review the existing gaps to be addressed when delivering gene-based care. RECENT FINDINGS: The factors contributing to the racial survival disparity are undoubtedly complex and likely an interplay between tumor biology, genomics, patterns of care and socioeconomic factors. Advances in genomic technologies that now allow for full characterization of germline DNA sequencing are integral in defining the complex and multifactorial cause of breast cancer and may help to explain the existing racial survival disparities. SUMMARY: Identification of inherited cancer risk may lead to cancer prevention, early cancer detection, treatment guidance, and ultimately has great potential to improve outcomes. Consequently, advances in HBC diagnosis and treatment without widespread implementation have the potential to further widen the existing breast cancer mortality gap between Black and NHW women.

The goal of our paper is to explore the role of AI in understanding health disparities in cancer care and its potential role in resolving them. Multiple studies have shown that with the recent advances in AI, its integration in cancer care has the potential to impact earlier diagnosis and improve clinical decision making. While AI risks to further widen health disparities, some studies suggest that it represents an excellent opportunity for resolving them. With active engagement, incorporating AI in breast cancer care represents an excellent opportunity for elucidating and resolving health disparities; however, without deliberate effort, it risks to further widen them.

Racial disparities in breast cancer are multifactorial and include inferior outcomes and increased rates of serious toxicity in African Americans. The purpose of this review is to evaluate the contribution of race, genetic ancestry, and genomic biomarkers to treatment toxicity and to demonstrate the impact of toxicity on racial disparities. Taxane-induced peripheral neuropathy (TIPN) and congestive heart failure (CHF) are potentially irreversible and life-altering toxicities of curative chemotherapy for breast cancer. Analysis of genetic ancestry, rather than self-reported race, in a large cooperative group adjuvant clinical trial discovered significantly higher rates of both TIPN and CHF in women of African descent compared with European Americans. Importantly, TIPN resulted in more dose reductions of chemotherapy in African Americans, which resulted in worse disease-free survival. Beyond race, significant individual variations in toxicity exist, which may be explained by validated genotypic predictors of TIPN and CHF, reviewed here. Race, in particular genetic ancestry, impacts both tumor and host biology, contributing to toxicity that drives disparities in quality of life and survival. Translating these data into clinical decision-making will benefit from engagement of the African American community to perform clinical trials and develop datasets focused specifically in this population to validate biomarkers and best understand patient preferences.

Detection of BRCA germline mutations (gBRCAm) impacts breast cancer medical treatment—according to differential sensitivity to cytotoxic chemotherapy and the activity of PARP inhibitors—and not only familial prevention. Guidelines for genetic testing—initially mainly based on familial history, age, and triple negative breast cancer (TNBC) subtype—currently are expanding in order to offer new therapeutic options. In the early setting, gBRCAm patients present a similar outcome as the non-carrier population with standard neoadjuvant chemotherapy, and the role of platinum chemotherapy is still a matter of debate. In metastatic setting, international guidelines recommend the use of platinum-based chemotherapy in gBRCAm patients and more broadly in TNBC patients. Olaparib and talazoparib monotherapy are approved in metastatic gBRCAm breast cancer. To date, it remains unclear how the combination of platinum-based regimen and PARP inhibitors should be sequenced.

PURPOSE OF REVIEW: Breast Self-Examination (BSE) remains controversial despite the 2009 United States Preventive Service Task Force (USPSTF) recommendation against teaching of BSE. The USPSTF recommendations were based on results from the Shanghai Study, high-quality randomized trial of BSE in 266,064 Chinese factory workers from 1989-1991; women instructed in BSE did not have a significant difference in mortality versus uninstructed controls. Regardless of the outcome of the Shanghai Study, the practice of BSE in the United States (U.S.) over the past 25 years has been associated with a marked reduction in the size of breast cancer identified by women. RECENT FINDINGS: In the Shanghai study, BSE was tested in China from 1989-1991. During this time period, Chinese breast cancer screening and treatment was not consistent with standard-of-care in U.S. and Europe. Breast cancer was a rare illness in China in the 1980’s. Treatment was not standardized; there was no breast imaging or margin assessment of the tumor. Tumor markers (e.g. estrogen receptor, progesterone receptor) were not reported. The Shanghai Study did not report in detail on the anti-cancer agents provided to women who enrolled in the trial. SUMMARY: BSE needs to be rigorously re-evaluated under current standard of care.

PURPOSE OF REVIEW: Standard options for the treatment of ductal carcinoma in situ (DCIS) include breast-conserving surgery (BCS) alone; BCS with radiotherapy or endocrine therapy, or both; and mastectomy. Survival is excellent with all options, but rates of local recurrence (LR) vary, as do quality-of-life measures. Here we discuss treatment outcomes, risk factors for LR, and tools for risk estimation. RECENT FINDINGS: After BCS, radiotherapy reduces the risk of LR by half, and endocrine therapy reduces the risk by a third. Young age, inadequate margins, and greater volume of disease are associated with higher risk of LR after BCS, while young age, high grade, and microinvasion are associated with higher risk of locoregional recurrence after mastectomy. Clinical tools, including the Memorial Sloan Kettering Cancer Center (MSKCC) DCIS nomogram, provide LR risk estimates after BCS that appear more accurate than current genomic assays. The safety of active surveillance for seemingly low-risk patients remains uncertain. SUMMARY: Estimation of LR risk, utilizing a multitude of clinicopathologic and treatment factors, can help a woman balance that risk with her values and priorities, and allow her to choose the optimal treatment option for her.

Mammographic screening and radiological surveillance for local management has led to an exponential increase in diagnosis of ductal carcinoma in situ (DCIS) with limited impact on breast cancer specific mortality. Since definitive diagnosis of DCIS requires histopathological examination increase in radiological surveillance has resulted in significant increase in breast biopsies. Pathological characteristics of DCIS include grade, necrosis, size, anatomy, margins of excision, estrogen, and progesterone receptor status, and these features are useful for both prognostication and prediction. Differential diagnosis of DCIS extends from atypical ductal hyperplasia to micro-invasive carcinoma and increasingly pathologists recognize intraductal lesions at the borderline between atypical ductal hyperplasia and ductal carcinoma in situ. Clinicopathological characteristics of DCIS continue to be significant in prospective trials and have been integrated with predictive molecular tools. Since most cases of DCIS do not progress to invasive cancer multiple tools which include clinicopathologic and molecular signatures are in the process of development and validation for personalizing treatment strategies for patients. Ongoing clinical trials are testing whether DCIS with favorable clinicopathologic characteristics may avoid loco-regional therapy which typically includes breast conserving surgery and radiotherapy.

Ductal carcinoma in situ (DCIS) is commonly treated with radiotherapy as a part of breast-conserving therapy, though increasingly the use of routine radiation treatment is being questioned. The intent of this review is to summarize studies on the role of radiotherapy for DCIS, with an emphasis on more recent trials. While older randomized clinical trials have established a local control benefit for adjuvant radiotherapy following breast-conserving surgery in all patients including those with low-risk DCIS, these and subsequent studies have failed to demonstrate any survival benefit. Given the risks associated with radiotherapy, studies have aspired to demonstrate that subgroups of DCIS patients who derive less benefit from treatment may safely avoid adjuvant radiotherapy. Nomograms based on retrospective analyses have been employed to help identify patients for omission of radiotherapy, and genomic assays as a proxy for tumor biology are being explored as strategies for patient selection. When patients do receive radiotherapy, radiation options such as hypofractionation, inclusion of a radiation boost to the resection cavity, and partial-breast irradiation are considerations to help individualize treatment. Finally, initial treatment for DCIS may have implications for subsequent therapy in the setting of salvage therapy for recurrent breast cancer. More recent studies on DCIS have aimed at identifying subgroups of DCIS patients who may safely omit radiotherapy and strategies to individualize radiation treatment of DCIS. Radiotherapy for DCIS should be a decision made after a careful discussion between physicians and patients, taking into account individual patient characteristics and preferences.

Breast Ductal Carcinoma in Situ (DCIS) is an increasingly common diagnosis and already accounts for ~20% of screen-detected breast cancers. A subset of patients with DCIS will experience disease recurrence and some will die from breast cancer. Tailored strategies for treatment are lacking at this time. Human Epidermal Growth Factor Receptor 2 (HER2) is a tumor associated antigen that is shown to correlate with poorer outcomes among patients with early breast cancer, including DCIS. Significant interactions between the humoral and cellular branches of the immune system were observed in tumorigenesis of HER2-expressing lesions. These can be leveraged through administration vaccines to improve outcomes among patients with HER2+ DCIS. Pre-clinical and clinical data support that immune response supported not only by CD8+ cytotoxic T cells but also CD4+ helper T cells can lead to antitumor activity in DCIS. These early studies have demonstrated prolonged, broad, activation of the immune system, and with a favorable toxicity profile. As nuances in our understanding of immune responses to early breast cancer begin to unveil, there is growing momentum in the development of preventative strategies. Clinical trials assessing the efficacy of vaccines for the treatment of DCIS are forthcoming.

This paper summarizes key issues pertinent to oncologic and surgical outcomes of risk-reducing mastectomy and reconstruction. Among BRCA 1/2 mutation carriers who present with initial breast cancer, risk-reducing mastectomy in patients who are young at time of initial breast cancer diagnosis have the greatest absolute reduction in contralateral breast cancer risk associated with contralateral risk-reducing mastectomy. Although retrospective studies are suggestive of a survival advantage conferred by risk-reducing mastectomy in BRCA ½ carriers, additional research in the contemporary era of magnetic resonance screening is necessary. A wide variety of reconstructive options are available after risk-reducing mastectomy. Long-term patient-reported outcomes favor autologous tissue reconstruction techniques. The decision for risk-reducing surgery and mastectomy reconstruction in patients with increased genetic propensity for breast cancer is multifaceted, with multiple factors pertinent to consideration including type of mastectomy, timing, and method of reconstruction. Shared informed decision making is critical to optimize outcomes. Appropriate patient counseling based on growing evidence regarding patient-reported outcomes should be provided in order to tailor therapeutic recommendations.

We aim to review the appearance of ductal carcinoma in situ (DCIS) across the spectrum of imaging modalities used in common clinical practice. Changes in technology and clinical breast cancer screening patterns have impacted the imaging evaluation of DCIS. DCIS classically presents as asymptomatic calcifications in women undergoing screening mammography. The replacement of traditional 2D mammography with digital breast tomosynthesis has changed the typical appearance of screen-detected DCIS. Ultrasound is traditionally utilized to detect DCIS in women with clinical symptoms, but efforts to increase screening ultrasound rates for women with dense breasts makes it more important to identify the appearance of DCIS in asymptomatic women. Improvements in MRI technology have made MRI the most sensitive imaging modality to detect DCIS and define the extent of disease, which is increasingly important given greater utilization of MRI for high-risk screening and determination of extent of known disease. Finally, the emergence of active surveillance, or non-surgical management, for DCIS has increased the focus on presurgical identification of associated invasive cancer, with early results demonstrating promise via computer vision and deep learning approaches for this task. DCIS has a highly variable imaging appearance which is subject to changes in imaging technology and clinical management.

As radiation therapy is used as an adjuvant treatment in an increasing number of women during the management of breast cancer, radiation therapy and its well-known adverse effects pose additional challenges for breast reconstruction. The purpose of this review is to examine recent data on outcomes of various breast reconstruction methods in the setting of radiation therapy and help surgeons and oncologists as well as patients with their decision-making process. Breast reconstruction methods can be categorized into autologous-, implant-, and tissue expander/implant-based, each with its distinct advantages and disadvantages. Autologous and tissue expander/implant are preferred when radiation therapy is expected based on surgical, aesthetic, and patient satisfaction. Use of latissimus dorsi flaps and acellular dermal matrix with tissue expander/implant has shown several advantages to traditional methods. For patients who have a high likelihood of requiring postmastectomy radiation therapy, choosing a breast reconstruction method depends on multiple factors. Patients and surgeons should be aware of the impact of radiation therapy so that they can make a well-informed decision.

Immune checkpoint inhibitors (ICIs) are an emerging therapy in breast cancer, but not all patients will have benefit with these medications. It has been proposed that certain gut microbes may play a role in protecting the host against inappropriate inflammation and modulating the immune response. Here, we review the current evidence on the association of the gut microbiome, antitumor immunity, and response to immunotherapy and discuss open questions, ongoing trials, and future directions for modulating the gut microbiome as part of breast cancer treatment. Several groups have showed that the composition of gut microbiota modulates responses to ICI in preclinical cancer models, and the composition of gut microbiota can predict which patients with solid tumors are more likely to respond to ICI. In addition, it was also showed that fecal microbiota transplant was able to make non-responder animals into responders when they received feces from patients who had benefited to ICI. Recent studies suggest that ICIs can be active in breast cancer but identifying the patients who are most likely to benefit remains a challenge. In other tumor types, the gut microbiome differs between responders and non-responders, suggesting that it can be used as a predictive biomarker of response. In addition, future investigations will determine whether manipulating the gut microbiota can improve responses to ICIs in breast cancer.

A systematic review of three databases (PubMed, Scopus, and Google Scholar) was conducted to appraise the current evidence behind the diagnosis and management of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). The goal is to help patients make informed decisions regarding reconstruction after breast cancer treatment by educating physicians on the nuances of diagnosis and treatment of BIA-ALCL. Following recent statements by the FDA, BIA-ALCL has recently garnered the attention of both patients and plastic surgeons. To date, BIA-ALCL has been almost exclusively associated with textured implants. BIA-ALCL is a very rare T cell lymphoma that was first described more than 20 years ago. BIA-ALCL usually follows an indolent course and carries an excellent prognosis if treated promptly. However, the pathogenesis of the disease is unclear, and further studies need to be conducted to better understand the disease.

Purpose of Review To explain the role of African American survivor advocates in addressing breast cancer disparities. Recent Findings The Sisters Network, Inc. is a national African American survivor advocates organization, founded in Houston Texas in 1994 and active today via affiliate chapters throughout the United States as well as its national headquarters. The Sisters Network provides essential outreach, educational, and research support to the breast oncology community. Summary The breast oncology community should partner with the Sisters Network and support their activities in efforts to achieve breast health equity.

Purpose of Review Across the world, medical training has been affected by the COVID-19 virus and this has changed the way physicians are educated. What is less clear is the effect of the pandemic on breast surgical oncology fellows who were in training during this time. This review discusses the experience of breast surgical oncology fellows during the pandemic and how fellowships adapted to preserve the educational experience and conserve the quality of training. Recent Findings The challenges and changes experienced by breast surgery fellows during the COVID-19 pandemic have proved to be sudden shifts in not only fellowship training, but future patient care and research opportunities, all while confronting the global impact of a deadly pandemic. While experiences between fellowships varied, the similarities and differences encountered highlight the regional and temporal differences in how fellowships responded to the pandemic. Summary Breast surgical oncology fellowship is one year long, with every day allocated to ensure the surgeon has a deep understanding of the multidisciplinary approach to this ever-evolving field. As the pandemic spread and affected different regions with varying severity, elective cases were canceled, resources were re-allocated, and uncertainty abounded. At the same time, novel approaches to fellowship training were rapidly implemented. It will take time and additional research to fully understand the long-term consequences for trainees affected during their breast surgery fellowship.