Blog

• Disease located in the inferior hemisphere of the breast:
  • Can be easily incorporated into a Wise pattern reduction mammoplasty

• Split reduction techniques:
  • Are best used for disease located in the upper inner or upper outer quadrants requiring skin excision due to the proximity of the tumor to the skin
  • With a split reduction technique:
    • The lateral (for upper outer quadrant cancers) or medial (for upper inner quadrant cancers) triangle of the Wise pattern is not positioned at the base of the breast:
      • But instead advanced up onto the breast where the area of disease was removed
• Donut mastopexy:
  • Is best used in patients with grade 1 ptosis with the area of disease is located close to the nipple areolar complex

• The radial ellipse lumpectomy:
  • Is useful for lateral tumors
  • With this technique a radial ellipse of skin and breast parenchyma is excised full thickness
  • This technique however does not improve significant ptosis

• References
  • Savalia NB, Silverstein MJ. Oncoplastic breast reconstruction: patient selection and surgical techniques. J Surg Oncol. 2016;113(8):875-882.
  • Silverstein MJ, Mai T, Savalia N, Vaince F, Guerra L. Oncoplastic breast conservation surgery: the new paradigm. J Surg Oncol. 2014;110(1):82-89.
  • Anderson BO, Masetti R, Silverstein MJ. Oncoplastic approaches to partial mastectomy: an overview of volume-displacement techniques. Lancet Oncol.2005;6(3):145–57.
  • Clough KB, Ihrai T, Oden S, Kaufman G, Massey E, Nos C. Oncoplastic surgery for breast cancer based on tumour location and a quadrant-per-quadrant atlas. Br J Surg. 2012;99(1):1389-1395

• Donut mastopexy:
  • Is best used to address small to medium cancers centrally located in any quadrant
• Results are best in patients with:
  • Grade 1 ptosis with enlarged nipple areola complex
• This approach in patients with significant ptosis:
  • Will result in flattening of the central breast and would be better treated with other onocoplastic techniques
• Treatment of triple negative breast cancers:
  • Should consider neoadjuvant chemotherapy prior to surgical excision
• Young patients with triple negative breast cancer:
  • Also should consider hereditary risk assessment:
    • As this may alter their decision regarding breast conservation
• Patients with a history of prior breast cancer treated with adjuvant radiation therapy:
  • Should not consider breast conservation unless there are special circumstances
• References
  • Savalia NB, Silverstein MJ. Oncoplastic breast reconstruction: patient selection and surgical techniques. J Surg Oncol. 2016;113(8):875-882.
  • Piper M, Peled A, Sbitany H. Oncoplastic breast surgery: current strategies. Gland surg. 2015;4(2):154-163.
  • Clough KB, Kaufman GJ, Nos C, Buccimazza I, Sarfati IM. Improving breast cancer surgery: a classification and quadrant per quadrant atlas for oncoplastic surgery. Ann Surg Oncol 2010;17(5):1375-1391.
  • Omarini C, Guaitoli G, Pipitone S, Moscetti L, Cortesi L, Cascinu S, et al. Neoadjuvant treatments in triple-negative breast cancer patients: where we are now and where we are going. Cancer Manag Res. 2018;10:91-103.

• In general, patients with significant ptosis of the breast:
  • Obtain better cosmetic results with a reduction mammoplasty compared to donut or Benelli mastopexy
• Lesions distant to the nipple areolar complex:
  • Can be difficult to access through a mastopexy incision

• References
  • Lebovic GS. Oncoplastic surgery: a creative approach to breast cancer management. Surg Oncol Clin N Am. 2010;19(3): 567-580.
  • Piper M, Peled A, Sbitany H. Oncoplastic breast surgery: current strategies. Gland Surg. 2015;4(2):154-163.
  • Clough, KB, Kaufman, GJ, Nos, C, Buccimazza, I, Sarfati, IM. Improving breast cancer surgery: a classification and quadrant per quadrant atlas for oncoplastic surgery. Ann Surg Oncol. 2010;17(5):1375-1391.
  • Clough KB, Benyahi D, Nos C, Charles C, Sarfati I. Oncoplastic surgery: pushing the limits of breast-conserving surgery. BreastJ. 2015;21(2):140-146.

• A recent study by Liang et al:
  • Showed that in patients undergoing contralateral breast procedures at the time of oncoplastic breast-conserving surgery:
    • 16.5% were found to have high-risk pathology in the contralateral breast:
      • With almost 5% of these being cancer
  • Larger studies from Europe have shown the contralateral occult malignancy rate:
    • To be 1% to 5%:
      • This rate of occult disease is higher than the reported occult malignancy rate in patients who are undergoing cosmetic reduction mammoplasty
  • Orientation of the specimen(s) from symmetry procedure may be beneficial when performing these operations in the setting of cancer treatment
• References
  • Liang Y, Muse-Fisher C, Rambukwella M, Naber SP, Chatterjee A. Malignant and high-risk lesions in the contralateral breast symmetry mastopexy and reduction specimens when performing large-volume displacement oncoplastic surgery. Ann Plast Surg. 2019;82(4S Suppl 3):S185-S191.
  • Sorin T, Fyad JP, Pujo J, Colson T, Bordes V, Leroux A, et al. Incidence of occult contralateral carcinomas of the breast following mastoplasty aimed at symmetrization. Ann Chir Plast Esthet. 2014;59(2):e21-e28.

• Use of oncoplastic surgery has become more common in the surgical treatment of breast cancer
• Multiple studies have compared the surgical complication rates between standard breast-conserving surgery with oncoplastic breast-conserving surgery
• A recent systematic review reported overall low rates of perioperative complications in patients who have undergone oncoplastic breast conserving surgery
• Studies comparing oncoplastic breast-conserving surgery to standard breast-conserving surgery:
  • Have reported:
    • Lower rates of post-operative seroma formation
    • No difference in surgical site infection
    • Lower positive margin and re-excision rates
  • Additional reports have shown this same low risk of perioperative complications in the obese population:
    • Making oncoplastic surgery an option even in obese women
• References
  • Carter SA, Lyons GR, Kuerer HM, Bassett RL Jr, Oates S, Thompson A, et al. Operative and oncologic outcomes in 9861 patients with operable breast cancer: single-institution analysis of breast conservation with oncoplastic reconstruction. Ann Surg Oncol. 2016;23(10):3190-3198.
  • De La Cruz L, Blankenship SA, Chatterjee A, Geha R, Nocera N, Czerniecki BJ, et al. Outcomes after oncoplastic breast-conserving surgery in breast cancer patients: a systematic literature review. Ann Surg Oncol. 2016;23(10):3247-3258.
  • Tong WM, Baumann DP, Villa MT, Mittendorf EA, Liu J, Robb GL, et al. Obese women experience fewer complications after oncoplastic breast repair following partial mastectomy than after immediate total breast reconstruction. Plast Reconstr Surg. 2016;137(3):777-791

• Diagnosis of a breast cancer during pregnancy requires a complex treatment plan with multiple multidisciplinary providers:
  • From both oncology and obstetrics:
    • Coordinating the timing of cancer treatment and the delivery of a high-risk pregnancy
• Gestational or pregnancy-associated breast cancer:
  • Refers to any breast cancer diagnosed:
    • During pregnancy or within the first year after childbirth
  • This is a rare diagnosis:
    • Yet remains the most common cancer in pregnant women:
      • Affecting approximately 15 to 35 per 100,000 deliveries:
        • Approximately 0.05%
• The majority of pregnancy-associated breast cancers are:
  • Ductal in origin, more likely to be poorly-differentiated, ER negative, PR negative and HER2-positive:
    • Compared to non-pregnant women, and present at advanced stages
• Evaluation of a dominant breast mass should include:
  • Ultrasound and mammogram with fetal shielding, and core biopsy
• Interpretation of mammography can be difficult in the highly dense tissue of pregnant women
• Use of MRI during pregnancy is both contraindicated and unhelpful:
  • Gadolinium contrast may cause fetal harm during the first trimester and is typically avoided
• Although the majority (approximately 80%) of breast biopsies in pregnant women will be benign:
  • It is critical that malignancy be ruled out
• Fine needle aspiration during pregnancy is associated with a higher rate of false positive and false negative results, without receipt of tumor markers:
  • Therefore core biopsy is recommended
• Staging should be performed in women with advanced disease, and in those with symptoms concerning for metastases:
  • This should include chest radiograph with fetal shielding, liver ultrasound or MRI without contrast, and “low-dose” radionuclide bone scans
• When possible, treatment of pregnancy-associated breast cancers:
  • Should follow similar guidelines to non-pregnant patients, and if at all possible, the pregnancy should be carried to term
• Systemic treatment of breast cancer during pregnancy involves special consideration of both the mother and baby
• Surgery is safe at all stages
• Chemotherapy:
  • Can be delivered from 14 weeks of gestation following completion of organogenesis through 35 weeks:
    • When it should be stopped to avoid leukopenia in preparation for delivery
  • Data from a single-institution prospective study indicates that:
    • FAC chemotherapy (5-FU, doxorubicin, and cyclophosphamide) is safe during the second and third trimesters
      • With fetal malformations approximating 1%
    • Experience with taxanes remained limited, but National Comprehensive Cancer Network (NCCN) guidelines:
      • Recommend weekly paclitaxel if warranted
    • Methotrexates:
      • Are contraindicated due to teratogenic side effects
    • Although 20% of pregnancy-associated breast cancers are HER2-positive:
      • Anti-HER2 therapy including trastuzumab has not been proven safe during pregnancy and is best delivered in the adjuvant setting:
        • MotHER a prospective U.S. registry, is evaluating women exposed to trastuzumab +/- pertuzumab during pregnancy or within 6 months of conception and following pregnancy outcomes and infants for the first month of life
      • Current recommendations suggest that targeted anti-HER2 therapy be delayed until after delivery
• Breast conservation:
  • Is not recommended if radiation would be timed during pregnancy because this is contraindicated:
    • However, it can be performed if radiation falls after delivery
• Axillary lymph node dissection was previously recommended:
  • But sentinel lymph node biopsy is feasible and should be offered
• Hormone therapy should be postponed until after childbirth
• Chemotherapy during pregnancy can cause concerns for the fetus which depend on the timing of drug administration:
  • Congenital malformations can occur in the first trimester
  • In the second and third trimesters prematurity, low birth weight and myelosuppression are the greatest concerns
• Among approved chemotherapy agents, long-term outcomes of children with in-utero exposure demonstrate normal development, cognition, and school performance when prematurity is controlled for
• References
  • Macdonald HR Pregnancy associated breast cancer. Breast J. 2020 Jan 14. doi: 10.1111/tbj.13714. [Epub ahead of print]
  • Goidescu I, Nemeti G, Caracostea G, Eniu DT, Chiorean A, Pintican R, Cruciat G, Muresan D. The role of imaging techniques in the diagnosis, staging and choice of therapeutic conduct in pregnancy associated breast cancer. Med Ultrason. 2019 Aug 31;21(3):336-343. doi: 10.11152/mu-1958. Review.
  • Alfasi A, et al. Breast Cancer During Pregnancy- Current Paradigms, Paths to Explore. Cancers. 2019; 11: 1669
  • National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Breast Cancer. Available with login at: https://subscriptions.nccn.org.
  • Gooch JC1,2, Chun J1, Kaplowitz E1, Guth A1, Axelrod D1, Shapiro R1, Roses D1, Schnabel F1. Pregnancy-associated breast cancer in a contemporary cohort of newly diagnosed women Breast J. 2019 Aug 25. doi: 10.1111/tbj.13510. [Epub ahead of print]

• In the preoperative setting:
  • Chemotherapy is typically recommended to improve breast cancer operability or downstage the axilla among medically fit patients
• Neoadjuvant endocrine therapy (NET) is a good option for post-menopausal women with ER+ breast cancers:
  • When aiming for improved candidacy for breast conservation or in patients in whom chemotherapy will not be safely tolerated
• Studies evaluating NET have demonstrated similar rates of clinical and radiographic response and breast conservation therapy (BCT) to those reported from studies using neoadjuvant chemotherapy
• When neoadjuvant chemotherapy (4 cycles of doxorubicin and paclitaxel) was compared directly to NET (12 weeks of aromatase inhibitors; exemestane or anastrozole):
  • NET was associated with comparable clinical response, higher rates of breast conservation (33% vs. 24%), and no difference in local recurrence at approximately 3 years
  • Meta-analysis and clinical trial data support use of aromatase inhibitors (letrozole or anastrozole) over tamoxifen, including:
    • Higher clinical and radiographic response rates (55% vs. 36%)
    • Improved rates of BCT (45% versus 35%)
  • The ACOSOG Z1031 trial demonstrated comparable effectiveness of exemestane, letrozole and anastrozole for 16 to 18 weeks before surgery
• NET requires a longer duration of treatment than preoperative chemotherapy and depends on the patient’s individual eligibility for breast conservation
• NET is typically recommended for 3 to 6 months prior to surgery; however, extended treatment for up to 12 months has been safe and is associated with a greater response to treatment
• Although tumor progression is rare on NET, continued surveillance is important for women with an intact primary breast tumor taking endocrine therapy, and cancer growth would be an indication for surgery
• The majority of clinical trials for NET have focused on postmenopausal women, in that younger patients often have higher-risk tumor biology and are likely candidates for chemotherapy:
  • Thus, data on the use of NET in premenopausal patients are limited to phase II trials and include ovarian suppression plus aromatase-inhibitors (i.e., exemestane+goserelin).
• References
  • Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, et al. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007;110(2):244-254.
  • Ellis MJ, Ma C. Letrozole in the neoadjuvant setting: the P024 trial. Breast Cancer Res Treat. 2007;105(suppl 1):133-143.
  • Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter trial. Ann Oncol. 2001;12(11):1527-1532.
  • Smith IE, Dowsett M, Ebbs SR, Dixon JM, Skene A, Blohmer JU, et al. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol. 2005;23(22):5108-5116.
  • Cataliotti L, Buzdar AU, Noguchi S, Bines J, Takatsuka Y, Petrakova K, et al. Comparison of Anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the pre-operative “arimidex” compared to tamoxifen (PROACT) trial. Cancer. 2006;106(10):2095-2103.
  • Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM5-based intrinsic subtype—ACOSOG Z1031. J Clin Oncol. 2011;29(17):2342-2349.

• Among women with operable breast cancers at the time of diagnosis:
  • Neoadjuvant chemotherapy (NAC) is increasingly used to gain information about the tumor’s response to treatment:
    • With pathologic response rates:
      • Correlating with long-term prognosis
• The most accepted definition of pathologic complete response (pCR) includes:
  • No residual invasive disease in the breast or sampled axillary nodes:
    • Although this definition varies:
      • Residual in situ disease does not affect the risk of distant recurrence
• Response to preoperative treatment differs by:
  • Tumor biology:
    • With hormone-receptor positive breast cancer patients having the lowest overall pCR rate
• For some women with residual disease, including those with HER2-positive and triple-negative breast cancers:
  • This allows for use of additional adjuvant therapy that improves cancer outcomes including receipt of:
    • TDM-1 (trastuzumab emtansine, KATHERINE Trial)
    • Xeloda (CREATE-X Trial)
    • Eligibility for ongoing clinical trials
• Notably, recent changes to the American Joint Committee on Cancer Staging System includes:
  • Pathologic stage after neoadjuvant chemotherapy as part of the updated system:
    • When pCR is achieved in both the breast and axillary nodes:
      • Survival is driven by response to chemotherapy compared to initial presenting stage
• Choosing a NAC regimen depends on tumor biology:
  • In HER2-positive patients:
    • Chemotherapy should be combined with HER2-targeted therapies:
      • i.e., taxane + carboplatin + trastuzumab, pertuzumab (TCHP)
  • For HER2-negative patients:
    • Anthracycline-based drugs including doxorubicin and cyclophosphamide followed by a taxane
    • Higher risk HER2-negative breast cancers (node-positive hormone-receptor positive patients and triple-negative patients) typically receive anthracycline and taxane-based regimens with or without carboplatin
  • Notably, results from the CALGB40603 trial suggested that for triple-negative breast cancer:
    • The addition of carboplatin to NAC resulted in a 14% increase in eligibility for breast conservation
• References:
  • Fayanju OM, et al. The Clinical Significance of Breast-only and Node-only Pathologic Complete Response After Neoadjuvant Chemotherapy. Annals of Surgery. 2018; 268(4): 591-601.
  • von Minckwitz, G et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. NEJM. 2018; 380(7): 617-628.
  • Masuda N, et al. Adjuvant Capecitabine for Breast Cancer After Preoperative Chemotherapy. NEJM. 2017; 376:2147-59.
  • Golshan M, et al. Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance). Annals of Surgery. 2015; Sep; 262(3):434-9.

• The brain is frequently reported as the first site of relapse:
  • In women with HER2-positive breast cancer treated with trastuzumab
• It is known that up to 50% of patients with HER2 positive metastatic breast cancer:
  • Will develop brain metastasis
• References
  • Pestalozzi BC, Zahrieh D, Price KN, et al. Identifying breast cancer patients at risk for Central Nervous System metastases in trials of the International Breast Cancer Study Group (IBCSG). Annals of oncology : official journal of the European Society for Medical Oncology. 2006;17(6):935-944.
  • Pestalozzi BC, Holmes E, de Azambuja E, Metzger-Filho O, Hogge L, Scullion M, et al. CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol. 2013;14(3):244-248.

• The CDK 4/6 inhibitors are a class of oral drugs that have been approved for HR+, HER2-negative metastatic breast cancer in the first-line setting or after progression on prior aromatase inhibitor
• In the MONALEESA-3 trial:
  • Ribociclib in combination with fulvestrant:
    • Showed progression-free survival (20.5 months vs. 12.8 months) and overall survival benefit over fulvestrant alone in HR+, HER2-negative metastatic breast cancer that was either treatment naïve or had up to one prior line of endocrine therapy
• Everolimus is an mTOR inhibitor with evidence of benefit in the metastatic setting after prior aromatase inhibitor:
  • However it is FDA-approved in combination with exemestane per the BOLERO-2 trial
• In the metastatic setting:
  • Radiation is generally pursued to palliate symptoms or control isolated disease that is not responding to systemic therapy
• References
  • Slamon DJ, Neven P, Chia S, Fasching PA1, De Laurentiis M1, Im SA, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018;36(24):2465-2472.
  • Slamon DJ NP, Chia S, et al. Overall survival (OS) results of the phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC) treated with fulvestrant (FUL) + ribociclib (rib). Paper presented at: ESMO; September 27 to October 1, 2019, 2019; Barcelona, Spain.
  • Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N Engl Med. 2011;366(6):520-529