Early-Stage (I–II) Breast Cancer
Background
What histologic subtypes of IDC are associated with favorable outcomes?
Tubular, medullary, mucinous (colloid), and papillary
What are the classic histologic features of medullary carcinoma of the breast?
Medullary carcinoma of the breast shows a syncytial growth pattern of poorly differentiated tumor with a high mitotic rate. There is often a prominent lymphoplasmacytic reaction involving at least 75% of the periphery and present diffusely throughout the tumor. Medullary carcinoma of the breast is managed the same as IDC.
What is a phyllodes tumor of the breast?
Previously known as cystosarcoma phyllodes, phyllodes tumor ranges from benign to malignant and is a rare tumor with leaflike, lobulated appearance on microscopic section. It has both malignant epithelial and stromal components; the stromal component has the potential for metastatic spread. There is LN spread in 10% of cases, so there is a need for axillary dissection. Surgery is the preferred management. RT is used only for rare +margin and possibly large (>2 cm) tumors treated by breast conservation surgery (BCS).
What is Paget Dz of the breast? What is the clinical presentation?
Paget Dz of the breast is caused by malignant epithelial cells (Paget cells) infiltrating the epidermis through mammary ductal epithelium. The clinical presentation is crusting, scaling, itching, and redness on the skin of the nipple that can progress to ulceration and bleeding.
What % of Paget Dz is associated with an underlying breast cancer (invasive ductal carcinoma [IDC] or ductal carcinoma in situ [DCIS])?
>95% of Paget Dz is associated with underlying breast cancer, with 90% being IDC and 10% being DCIS.
What % of invasive cancers are lobular carcinomas?
5%–10% of invasive cancers are lobular carcinomas.
What % of lobular carcinomas are associated with contralat and synchronous primaries?
Up to 30% of lobular carcinomas are contralat synchronous and metachronous primary tumors.
Of the pts with early-stage breast cancers who will ultimately have recurrence, what % recurs after 5 yrs of follow-up?
According to the 25-yr follow-up of NSABP B04 (Fisher B et al., NEJM 2002), 25% of women fail distantly after 5 yrs, and 50% of women fail in the contralat breast. This supports the need for long-term follow-up.
According to the NSABP B04 trial, what % of women with a clinically– axilla were found to have axillary mets at LND?
Per NSABP B04, 40% of these women had axillary mets at LND.
Of the women who had a clinically– axilla and did not have a nodal dissection, what % eventually developed a clinically+ axilla?
20% of these women developed a clinically+ axilla.
Workup/Staging
What is the size cutoff to be considered a microinvasive Dz in the primary breast tumor?
A primary breast tumor >0.1 cm is considered microinvasive Dz.
What is the workup for invasive breast cancer?
Invasive breast cancer workup: H&P (inquire about family Hx of breast or ovarian cancer, Hx of atypical ductal or lobular hyperplasia), CBC, CMP, bilat mammogram, estrogen receptor (ER)/progesterone receptor/HER2 status, and β-HCG (if premenopausal). If stage >IIA, then bone scan. Otherwise, imaging for suspicious Hx, physical, or lab findings.
List the subsets of stage I breast cancers (T1mic– T1a-c).
T1mic: ≤ 0.1cm;
T1a: >0.1 but ≤0.5 cm
T1b: >0.5 cm but ≤1 cm
T1c: >1 cm but ≤2 cm
All stage I tumors are node–.
What is the TNM staging for stage II breast cancers?
T2N0, T1-2N1, T3N0
T2 has tumors >2 cm but ≤5 cm; N1 has 1–3 +nodes. T3 has tumors >5 cm.
How are pN1(i+) and pN1mi defined for the involvement of breast cancer cells in the axillary LNs?
Based on the size of micrometastasis.
pN1(i+): isolated tumor cells (ITCs) that are immunohistochemistry or hematoxylin and eosin (H&E) positive but ≤0.2 mm
pN1mi: mets >0.2 mm and/or >200 cells but ≤2 mm
Are pN1(i+) counted for the total number of positive involved LNs?
No. ITCs in LNs are not excluded from a total +node count for purposes of N classification.
What % of breast cancer pts are diagnosed with stage I–II Dz?
~75% of breast cancer pts are diagnosed with stage I–II Dz. (Osteen RT & Karnell LH, Cancer 1994)
What is the T stage for Paget Dz of the breast?
The T stage for Paget Dz is Tis, but only if it is not associated with an underlying noninvasive (i.e., DCIS and/or lobular carcinoma in situ) or invasive cancers.
How should Paget Dz associated with an underlying breast cancer be staged?
Per the AJCC 7th edition (2009), Paget associated with underlying breast cancer should be staged according to the T stage of the underlying cancer (Tis, T1, etc.).
Treatment/Prognosis
What are the management options for early-stage breast cancers?
Early-stage breast cancer management options:
Modified radical mastectomy +/− chemo +/− RT
Breast conservation therapy (BCT = BCS + RT) +/− chemo
Consider endocrine therapy for all women with ER+ tumors (even for T1a tumors) for risk reduction and to diminish the small risk of Dz recurrence.
When should adj chemo be utilized in the management of early-stage breast cancers?
Adj chemo is recommended for tumors > 1 cm and T1b tumors that are ER– +/− HER2. As well, it can be considered for 0.6–1-cm tumors that are grade 2 or 3 or + LVI. For ER+ tumors with ≥T1c Dz (including T2–T3), consider using Oncotype DX to determine the risk score for the benefit of chemo. However, the benefits of chemo are not certain for pts >70 yrs of age.
What systemic therapy is recommended for pts with ER+ tumors that are <1 cm?
Endocrine therapy would be the recommended systemic therapy without chemo.
What are some general principles of administering adj endocrine therapy?
General principles for administration of adj endocrine therapy:
If the pt is premenopausal, tamoxifen (20 mg/day) is given for 5 yrs. If the pt remains premenopausal, therapy ends. However, if the pt becomes postmenopausal, aromatase inhibitors (AIs) × 5 yrs are added.
If the pt is postmenopausal, AI × 5 yrs or tamoxifen × 2–3 yrs or 4.5–6 yrs → AI × 5 yrs is recommended.
Tamoxifen × 5 yrs is given for any pts who are intolerant, refuse, or have contraindications for AIs. (NCCN 2010)
What are the contraindications for the use of AIs?
Premenopausal status or the use of HRT in postmenopausal women
What are the major side effects of tamoxifen and AIs?
Tamoxifen: small increase in blood clots, strokes, uterine cancer, and cataracts
Aromatase inhibitors: bone loss and osteoporosis, joint pain and stiffness, and hypercholesterolemia. Bone mineral density should be monitored. Consider bisphosphonates or statin drugs to counter the effects.
When should paclitaxel (T) be added to Adriamycin/cyclophosphamide (AC) chemo?
T should be added for node+ pts. AC × 4 cycles can be used alone for >1 cm, –node tumors. AC followed by T should be administered in a dose-dense fashion (q2wks), or AC q3wks → weekly T × 12 wks.
Drug doses: Adr, 60 mg/m2 intravenously day 1; cyclophosphamide, 600 mg/m2 intravenously day 1; T, 175–225 mg/m2 by 3-hr intravenous infusion day 1 q21days, or 80 mg/m2 by 1-hr intravenous infusion weekly × 12 wks.
What systemic therapies are recommended for HER2+ tumors?
Systemic therapies for HER+ tumors:
If the tumor is <5 mm and a –node, just give endocrine therapy (if ER+).
If the tumor is 0.6–1 cm and a –node, consider combination chemo +/− trastuzumab (Herceptin).
If the tumor is >1 cm, add combination chemo with Herceptin.
Combination chemo + Herceptin is recommended for all node+ pts. The preferred combination chemo with Herceptin is Taxotere/carboplatin/Herceptin (TCH): Taxotere (75 mg/m2 intravenously day 1), carboplatin (AUC 6 intravenously day 1), q21days × 6 cycles, and Herceptin (4 mg/kg on wk 1 → 2 mg/kg × 17 wks → 6 mg/kg q3wks until 1 yr elapses). B/c of synergistic cardiotoxicity of traditional AC-TH, TCH is preferred.
How should trastuzumab (Herceptin) be used in the management of early-stage breast cancers?
Trastuzumab can be used in pts with HER2+ tumors > 1 cm. T1a-T1b tumors that are node– have a good prognosis even with HER2 amplification. This cohort is not well studied in randomized trials; therefore, the potential long-term cardiac morbidity risks with uncertain Dz control benefits should be weighed before using trastuzumab.
If trastuzumab is added to the Tx of BCT for early-stage breast cancers, how is it administered?
Trastuzumab is added after completion of Adr-based chemo, but it can be administered with Taxol or Taxotere at 4 mg/kg with the 1st dose of Taxol. Trastuzumab is given on a weekly basis (2 mg/kg) for 1 yr and can be given concurrently with RT. If capecitabine is added as an RT sensitizer, trastuzumab can also be given concurrently.
What data supports BCT (lumpectomy + radiotherapy) having equivalent survival outcomes to mastectomy +/+ LND?
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